The two stars were photographed on the set of the Netflix film in Oahu, Hawaii on Monday.
Aniston, 52, wore a green top and flower-patterned skirt while Sandler, 55, wore a blue button-down shirt and blue pants.
Sandler and Aniston are returning to their characters Nick and Audrey Spitz, respectively, after the first film debuted on Netflix in 2019.
Murder Mystery follows, Nick, a New York cop, and Audrey, his wife, as they go on a European vacation to reinvigorate their marriage when a chance encounter leads to them both being framed for the murder of an elderly billionaire.
In September, TV Line reported the sequel would be "another international adventure full of intrigue and hijinks."
Scott Yamano/Netflix Jennifer Aniston and Adam Sandler in Murder Mystery
In June 2019, Netflix said the first movie had been viewed by over 30 million accounts in three days.
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At the time, the streamer said the movie's debut was "the biggest opening weekend ever for a Netflix film."
Murder Mystery is the second movie Aniston and Sandler have made together, following the 2011 romantic comedy Just Go With It. With the sequel, the two friends are making their third movie together.