The loss drops the Quakers to the loser's bracket, where they will face the loser of tonight's Mississippi State vs. St. John's contest in an elimination game on Saturday at noon.
The Cavaliers' win was highlighted by a three-run blast from Henry Godbout in the second inning.
The Quakers responded in the fourth with RBIs from Davis Baker and Nick Spaventa, but that was as close as they would get.
Zaffiro surrendered three runs on four hits over six innings, walking four and striking out four. Eli Troop gave up one run in two innings of relief.
Penn's offense struggled, mustering just four hits in the contest. Wyatt Henseler had a tough game, finishing 0-for-4 with three strikeouts.
