Principal photography of season one was interrupted in March 2020 due to the COVID-19 pandemic. After several months off, they resumed shooting in New York City in August and finished in October, making it one of the first productions in the world to finish filming during the COVID-19 pandemic with new safety protocols.
HBO Max renewed the show for a second season shortly after the first season finale.
Michiel Huisman said during an interview in April 2021 that Kaley Cuoco had difficulty filming sex scenes with him and he suspects it was because she had never filmed a passionate love scene during her career. She wasn't used to it and couldn't relax. He said, "...we're making out on the bed, under the covers, we're doing our first scene like that and I noticed she was sort of hovering on top of me, she's not really sitting on my legs. After like take three she starts to shake a little bit and I'm like 'Kaley, what are you doing? Just sit down!' And it turned out that she was so uncomfortable and she had no idea how to do this thing. She was trying not to touch me."
On Dax Shepard's podcast "Armchair Expert", Kaley Cuoco admits she optioned the rights to the book Flight Attendant by Christopher A. Bohjalian prior to reading it.
In the book it states that Cassandra Bowden watches an "old sitcom about brilliant young physicists who were socially awkward". Kaley Cuoco (who plays Cassandra Bowden) starred in The Big Bang Theory, a sitcom about socially awkward physicists.