Culpepper visited the Green Bay Packers on April 23 and 24, 2008. He would later turn down the offer from the Packers, $1 million for a one-year contract, claiming the deal was not good. He said he was in contact with a few other teams. In July 2008, it was reported that the Detroit Lions were interested in signing Culpepper, but they never made an offer to him. He worked out with the Pittsburgh Steelers in August 2008, but the Steelers elected to sign Byron Leftwich instead to replace the injured Charlie Batch. On August 29, 2008, Culpepper then changed his mind and stated that he would consider a backup role in Green Bay if they were still interested in him, but the team did not put forth an offer.
On September 4, 2008, Culpepper announced his retirement. He expressed his frustrations with the NFL in a brief retirement letter. The main reason of his retirement was because he felt he could still be a starting quarterback in the NFL.
On November 2, 2008, ESPN reported that he had agreed to terms on a two-year deal contract with the Detroit Lions and would join the team the following week. After passing a physical, Culpepper officially signed with the Lions on November 3. The Lions assigned Culpepper number 11, the number Roy Williams had worn before he was traded to Dallas on October 14. Culpepper played four games with the Lions before suffering a shoulder injury. On December 28, 2008, the Lions became the first team in NFL history to go 0–16. The only other teams since the AFL–NFL merger to have a winless season were the 1976 Tampa Bay Buccaneers, who went 0-14 (the NFL did not extend the schedule to 16 games until 1978), the 1982 Baltimore Colts, who went 0–8–1 during that strike-shortened season, and subsequently the 2017 Cleveland Browns, who went 1–31 over the 2016 and 2017 seasons.