The late-night host said he will resume putting out new episodes of TBS' "Conan" on March 30. His staff will remain at home, and the show will be cobbled together with O'Brien on an iPhone and guests via Skype.
"This will not be pretty, but feel free to laugh at our attempt," said O'Brien on Twitter.
The late-night shows have shut down production due to the coronavirus pandemic to avoid gathering live audiences and large TV crews. Some hosts have pumped out web videos.
Jimmy Fallon has produced 10-minute "At Home" shows for NBC's "Tonight." In one episode, he did a video chat with Lin-Manuel Miranda. Jimmy Kimmel and David Spade have given monologues from their homes. On Monday, Stephen Colbert delivered a 10-minute monologue from his bathtub in a segment that was added to an episode that was otherwise a rerun of CBS's "The Late Show."
O'Brien, though, is the first to try to remotely mount a full broadcast from home.
"The quality of my work will not go down because technically that's not possible," O'Brien joked in a statement.
For most people, the coronavirus causes only mild or moderate symptoms, such as fever and cough. For some, especially older adults and people with existing health problems, it can cause more severe illness, including pneumonia.
The vast majority of people recover from the virus.