One of 15 rhesus macaques infected with SIVsmm9 developed profound hemolysis with spherocytosis, reticulocytosis, and IgG and complement at the red blood cell surface. A female offspring born to this animal developed similar findings. Furthermore, cold agglutinins were noted in samples from both animals. Four of the 13 animals remaining in the cohort had weakly positive antiglobulin tests but were not anemic. Autoimmune hemolytic anemia may be an underrecognized cause of anemia in SIV infection.