Ohtani has been struggling with a blister on his hand picked up against the Oakland Athletics earlier this month.
The 23-year-old two-way phenom was withdrawn after just two innings on his next start – the 10-1 defeat against the Boston Red Sox.
The Angels let slip that Ohtani would pitch in the second game of their series against the Astros in their game notes.
He will come up against Houston star Justin Verlander.
Tyler Skaggs will start for Los Angeles in the first game on Monday while Nick Tropeano will pitch the third and final game.
Ohtani revealed on Friday that his blister was “recovering”.
He added: “I’m hoping to be able to pitch well in a game by taking care of it on a daily basis.”
Despite his blister woes, Ohtani has continued as the Angels’ designated hitter.
He is batting .342 with three home runs and 11 RBIs.