The Cardinals fell to the 8th-seeded Connecticut Huskies 3-2 in 12 innings on Wednesday.
After grabbing a 2-1 lead after in the first inning, the Cardinals couldn't find an offensive spark for the remainder of the contest. U of L managed just 3 hits for the next 11 innings.
Louisville now faces the difficult task of playing in the loser's side of the bracket in the double-elimination tournament.
U of L will face host South Florida on Thursday at 5:00pm.