With the loss, Saint Mary's drops to 4-7, while UC Riverside improves to 6-5.
Christopher Akmon had SMC's RBI, driving in Anthony Villa who had a leadoff double in the second inning.
UC Riverside tied it in the fourth inning with an unearned run. Patrick Keane (0-1) came on in relief to shut the door down on a possible big fourth inning by the Highlanders.
The score would remain tied until the eighth inning as a leadoff walk to the Highlanders triggered a rally. UCR would score three times and take the 4-1 lead.
The Gaels could not comeback in the ninth as UCR took the series.
Villa and Markus Melgosa led the Gaels with two hits apiece. Trevor Ellison, Akmon and Ricky Boas also had hits for SMC.
Ben Griset started for the Gaels and went 4.1 innings, allowing four hits, one run, none earned, walked four and struck out seven.
Keane went the rest of the game, going 3.2 innings and was solid except for the eighth inning. He finished giving up three runs on three hits, walking one and striking out four.
Saint Mary's is back in action on Monday when it takes on UC Santa Barbara on the Gaucho campus at 2:00 p.m.