And Friday, the Sox designated the right-hander for assignment.
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The team also announced it reinstated outfielder Eloy Jimenez from the bereavement list.
Santana went 0-2 with a 9.45 ERA in his three starts, giving up 14 earned runs in 13 1/3 innings with a 1.88 WHIP. He allowed six home runs.
Santana gave up four runs and six hits in 4 2/3 innings Wednesday in a 4-3 loss against the Orioles.
Santana was signed as a minor-league free agent on Feb.