Ohtani, who has provided one of the season's most compelling storylines after impressing as both a pitcher and a batter, was roughed up from the start as the Los Angeles Angels faced the Red Sox in Anaheim.
Ohtani gave up a leadoff homer to Boston's Mookie Betts, and he couldn't throw his formidable breaking pitches for consistent strikes in the first night start of his big-league career.
Boston scored five runs in the third inning thanks to homers by Bradley Jr., Holt and Betts, the first time they've hit three homers in the same inning since the 2012 season.
"(The blister) had an effect on the overall command of all his pitches", Angels manager Mike Scioscia said after the game.
"He didn't say anything in warm-ups about it".
Through two starts, Ohtani would compile 18 strikeouts to just two walks.
The Angels will continue their series with the Red Sox Wednesday night before the finale on Thursday.
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The Red Sox led 7-0 by the time Betts had his next at-bat. "I also felt the same way, but I tried to pitch today, and with the high intensity of the game, it didn't hold up too well".
"The medical people took a look at it, and they thought it would be fine for today", Ohtani said through an interpreter. "Obviously, this is a new wrinkle right now, with the blister coming up, but we'll get into that later in the week".
Scioscia also said he's optimistic Ohtani can make his next start on the mound.
"We have seen increases in social media, ratings in China, in Chinese Taipei and in Korea", Small added.
But as for Ohtani, all good things must come to an end. In his first two dazzling starts against the A's, Ohtani had a 70.3 percent whiff rate (26 whiffs on 37 swings) on his splitter.
At the plate, Ohtani has three home runs and 11 RBI in 30 at-bats.
The 25-year-old star went 3-for-3 (with two walks), with all of those hits being of the dinger variety in a 10-1 win over the Angels.