The 2010 Beef 'O' Brady's Bowl St. Petersburg was the third edition of the college football bowl game formerly known as the St. Petersburg Bowl. It was played at Tropicana Field in St. Petersburg, Florida, on Tuesday, December 21, 2010 at 8 p.m. (ET). The game was telecast on ESPN and featured the Southern Miss Golden Eagles from Conference USA versus the Louisville Cardinals from the Big East Conference. Louisville was a member of Conference USA from 1996 through 2004.

The Golden Eagles went to their ninth straight bowl game, the league's second longest active bowl streak. This was their first bowl trip to Florida in 29 years since playing Missouri in the 1981 Tangerine Bowl in Orlando. Although the 2010 season proved to be a successful one on the field for the Golden Eagles, sadly the most memorable public event was when three players were shot after a fight at a club spilled outside to the parking lot. Linebacker Martez Smith suffered the most serious injury, and is paralyzed from the waist down. The Golden Eagles went 1–1 following the tragic events, winning over Houston but losing a shootout to Tulsa.

Under first year coach Charlie Strong the Cardinals returned to their first bowl game since the end of the 2006 season when they appeared in the Orange Bowl. Louisville entered the contest with a 6–6 record after defeating Rutgers to become bowl eligible. The Cardinals' defense ranked 12th in the nation in total defense during the regular season. Louisville had gone to eight bowl games in nine years but had been absent from bowl play for the three seasons immediately preceding 2010.

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