During Comic-Con 2009, numerous sixth-season reports were made. Carlton Cuse stated both the time travel and flash-forward seasons were over, and they were moving into something different for the sixth season. Josh Holloway stated his character Sawyer would revert to his old self after the loss of Juliet. Though Cuse and Lindelof stated that the Dharma Initiative would no longer play a large role in the show, they have said that the "Dharma-Michigan connection" would play a significant role in season six. Lindelof stated that the producers had a direct hand in the production of the season six promotional poster that was first displayed at Comic-Con, and that everything in it was intentional; he also made a reference to the Abbey Road cover in connection to the poster. Season six was the first and only season of Lost ever to not feature any kind of preview or official promotional material such as sneak peeks and promo pictures for future episodes since the Lost producers considered any single frame from the first episodes to be too revealing. According to Lindelof, "even a single scene from the show would basically tip what it is we're doing this year, and what it is we're doing this year is different than what we've done in other years." Lindelof has also emphasized that the flashes-sideways are important, stating "People are saying [they] don't need these stories and all we can say is they're absolutely 100 percent necessary to tell the story of Lost, and hopefully by the end of the season it will be more obvious as to why." He also noted that the term "flash-sideways" was deliberately used instead of "alternate reality" because viewers might otherwise "infer that one of them isn't real, or one of them is real and the other is the alternate to being real." When asked to describe the last three episodes, Lindelof said "Water."
ABC charged advertisers $900,000 USD for a 30-second commercial during the series finale, in contrast to the standard 2010 season price of $214,000.
The cast features fifteen major roles with star billing: eleven return from the fifth season, one returns from the fourth season after a year's absence, and three are new regular cast members. Unlike the latter half of the previous season, in which the cast was divided into two groups following two separate storylines, Season Six features an alternate universe scenario which the producers call "flash-sideways," and almost all the main characters participate in both storylines. Returning from the fifth season are the survivors' leader Dr. Jack Shephard (Matthew Fox); former fugitive Kate Austen (Evangeline Lilly); millionaire Hugo "Hurley" Reyes (Jorge Garcia); former torturer Sayid Jarrah (Naveen Andrews); con artist James "Sawyer" Ford (Josh Holloway); medium Miles Straume (Ken Leung); former mob-enforcer Jin-Soo Kwon (Daniel Dae Kim) and his privileged wife Sun Kwon (Yunjin Kim); leader of the island's native population (known as the "Others") Ben Linus (Michael Emerson); and deceased crash survivor John Locke, who lives on in the sideways timeline but has been possessed in the original timeline by the mysterious Man In Black. Emilie de Ravin returns in her role as Claire Littleton, a new mother who was absent for one season after disappearing on the Island, and Henry Ian Cusick also returns as Desmond Hume, who starts the season off the Island. The new main cast roles go to pilot Frank Lapidus (Jeff Fahey), Richard Alpert (Nestor Carbonell), an ageless advisor to the Others, and mysterious Flight 316 leader Ilana Verdansky (Zuleikha Robinson). Carbonell was named a main cast member by the executive producers at Comic-Con 2009, after guest starring in the previous three seasons, and Fahey and Robinson were confirmed after appearing in recurring roles in the fourth and fifth seasons.
Several former cast members are scheduled to return to the show, or have been asked back. Elizabeth Mitchell returns as fertility specialist Dr. Juliet Burke. Mitchell has stated that her return is "instrumental to the story". Dominic Monaghan returned as rock star Charlie Pace in four episodes. Jeremy Davies returned as physicist Daniel Faraday in multiple episodes. Ian Somerhalder also returned as Flight 815 crash survivor Boone Carlyle in several episodes. Rebecca Mader, who portrays anthropologist Charlotte Lewis, also returned. The producers have also confirmed that Harold Perrineau and Cynthia Watros, who portray Michael Dawson and Libby Smith, respectively, returned in the second half of the season. About the return of Libby, Cuse stated, "Finally, all of your questions [about Libby] will be answered", however, Lindelof jokingly responded, "No, they will not". Michelle Rodriguez, another second season star, returned as police officer Ana Lucia Cortez, following a brief cameo in the fifth season. Maggie Grace, who portrays Shannon Rutherford, Boone's stepsister, was asked to return at the beginning of the season, but Grace was unable due to her schedule; she appeared later in the season, instead. Furthermore, the producers wished to bring back the character of Walt Lloyd, however Malcolm David Kelley, who portrays Walt, has aged significantly and the producers are working to overcome this obstacle.
Recurring characters who returned include: Jack and Claire's father, Dr. Christian Shephard (John Terry), wealthy industrialist and former Other Charles Widmore (Alan Dale), Desmond's wife Penny Widmore (Sonya Walger), former Other Eloise Hawking (Fionnula Flanagan), Locke's ex-girlfriend, Helen Norwood (Katey Sagal), Hurley's former boss, Randy Nations (Billy Ray Gallion), mysterious Flight 316 passenger Bram (Brad William Henke), Sayid's wife, Nadia (Andrea Gabriel), deceased Frenchwoman Danielle Rousseau (Mira Furlan), science teacher Leslie Arzt (Daniel Roebuck), the Others' doctor Ethan Rom (William Mapother), Ben Linus' father Roger (Jon Gries), mercenaries Martin Keamy (Kevin Durand) and Omar (Anthony Azizi), and Vincent, a dog who survived the crash of Flight 815 and lives on the island. Mark Pellegrino returns in his role as Jacob, the mysterious figure in charge of the island, while Titus Welliver also reprises his role as the mysterious unnamed character, known only as "The Man in Black", who appeared to be antagonistic to him in the season 5 finale. L. Scott Caldwell and Sam Anderson returned in their roles as Rose and Bernard respectively, as does Kimberley Joseph who plays 815 stewardess-turned-Other Cindy. Also, Academy Award-winner Fisher Stevens returns as communications officer George Minkowski from the first few episodes of the fourth season in the eleventh episode. Kevin Tighe returns as Anthony Cooper, Locke's father.
Several new recurring characters were introduced in the sixth season. "Deadwood" actor John Hawkes was cast to portray a character named Lennon and Japanese actor Hiroyuki Sanada obtained the role of ; both men are Others stationed at the temple. Also, William Atherton was cast in a guest role as the principal of the school where Ben works. Sheila Kelley has been cast in a recurring role that was initially described as "Kendall" and later confirmed to be "Zoe".