It was confirmed earlier this month that the actor will be taking a break from the CBS drama to receive "supervised treatment for prescription pain medication".
"Things happen, that's the business," executive producer Peter Lenkov told TV Guide. "We rewrote it."
O'Loughlin will appear briefly as Steve McGarrett in the show's April 9 episode 'Haʻalele', but will be entirely absent from the following episode, due to air on April 30.
The instalment missing McGarrett will feature guest stars Chris O'Donnell and LL Cool J as part of a crossover with fellow CBS series NCIS: Los Angeles.
O'Loughlin will then reappear in the May 7 episode and the May 14 second season finale.
Hawaii Five-0 was picked up for a third season earlier this month as part of an 18-show renewal by CBS. Michelle Borth, who plays McGarrett's love interest Catherine Rollins, has been promoted to series regular status for the new season.
> Hawaii Five-0 star Lauren German joins Chicago Fire pilot
Watch a clip from the last episode of Hawaii Five-0 below: