The Once Upon a Time star will play the latest patient of Hugh Laurie's maverick physician, according to TV Line.
"David's presence will change the course of the season," said executive producer Greg Yaitanes. "We are all fans of his work here at House and excited he is lending his talent to such a significant episode of our series."
The episode, directed by Yaitanes, will also star Casino Royale's Jeffrey Wright as a mentor of Foreman (Omar Epps).
Anders is best known for his roles in a number of cult shows, including The Vampire Diaries, 24, Heroes and Alias.
His House episode 'Nobody's Fault' is expected to air in early 2012. Two and a Half Men actress Melanie Lynskey has also signed up to appear on the medical drama.
House airs on Mondays at 9/8c on Fox in the US, and on Thursdays at 10pm on Sky1 in the UK.
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Watch a clip from this week's House below: