On June 5, 2016, Murphy was selected to his second all-star game. He was nearly voted a starter by fans, losing to the Cubs' Ben Zobrist by just 88 votes. In 142 games, Murphy finished the year with a .347 batting average, 25 home runs, and 104 RBI. He also led the NL in doubles (47), slugging percentage (.595), and on-base-plus-slugging (OPS) percentage (.985). He won his first Silver Slugger Award, being named the best offensive National League second baseman of 2016. He finished second in the NL MVP voting behind Kris Bryant. On September 20, 2016, Murphy was the last batter that Marlins pitcher José Fernández faced in the major leagues; Fernández died in a boating accident five days later.