The Lions traveled to the Edward Jones Dome to take on the St. Louis Rams, where in this game, Lions Offensive Coordinator Mike Martz would go up against his former team. Detroit fell behind early, as kicker Jeff Wilkins nailed a 42-yard and a 19-yard field goal to give the Rams an early lead. The Lions would get a field goal of their own, as kicker Jason Hanson got a 29-yard field goal. However, before the end of the period, St. Louis increased their lead with QB Marc Bulger completing a 16-yard TD pass to rookie TE Joe Klopfenstein. In the second quarter, Detroit would start to rally, as QB Jon Kitna and WR Mike Furrey connected on two touchdown passes (a 1-yarder and a 10-yarder). The Rams would trail by 1 at halftime, as Wilkins got a 46-yard field goal to end the half as the score was 17 to 16 Lions. In the third quarter, the points continued to climb, St. Louis would regain the lead with Bulger completing a 16-yard TD pass to WR Torry Holt. The Lions would respond with Hanson getting a 20-yard field goal and RB Kevin Jones running 35 yards for a touchdown. However, RB Steven Jackson would help the Rams respond with a 1-yard TD run. In the fourth quarter, Detroit would score again as Jones got a 7-yard TD run. That would be as far as the Lions would get in the game, as the Rams scored 10 unanswered points to end the game, as Wilkins nailed a 47-yard field goal, and Bulger connected with WR Isaac Bruce on a 5-yard TD pass. With their loss, the Lions fell to 0-4.

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