Karl Otto Stetter (born 16 July 1941) is a German microbiologist and authority on astrobiology.

The majority of Stetter's research has focused on sampling, isolating and characterizing archaeal organisms which comprise the third domain of life, particularly undiscovered extremely heat-loving (hyperthermophilic) bacteria and Archaea, also called extremophiles, growing optimally between 80 and 113 °C.

[1] Nanoarchaeum equitans, an archaeal microorganism containing the world's smallest known genome, was discovered by Stetter in 2002 in a hydrothermal vent off the coast of Iceland.

[2] Among the other extremophiles discovered by Stetter has been Pyrococcus furiosus,[3] which was found on the Italian island of Vulcano in 1981.

In 2003, Stetter was honored with the Leeuwenhoek Medal by the Royal Netherlands Academy of Arts and Sciences, an award given every 10 years to the scientist who has made the most outstanding contributions to the advancement of microbiology.