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Objectives Increased rates of infection with Toxoplasma gondii have been found in individuals with schizophrenia as compared to control groups but this issue has not been studied in mania. Methods We measured immunoglobulin G (IgG) and IgM class antibodies to T.gondii in 57 individuals with mania who were assessed at up to three time-points. We also measured these antibodies in 743 individuals in other psychiatric groups and in 314 non-psychiatric controls. T.gondii antibody levels were compared among groups by multivariate analyses. IgG class and IgM class antibodies to cytomegalovirus were also measured in the same samples. T.gondii antibody levels were also compared over time in the mania group. Results The mania group had a significantly elevated level of IgM antibodies to T.gondii as compared to the control individuals without a psychiatric diagnosis [odds ratio (OR)=2.33, pOR=2.32, pT.gondii were not found in individuals with the other psychiatric diagnoses. We also did not find an increased level of IgG class antibodies to T.gondii or IgG or IgM class antibodies to CMV in the individuals with mania. Within the mania group, there was a significant difference between the prevalences of increased levels of T.gondii IgM at the baseline and the follow-up time-point (t=2.97, p<0.003). Conclusions Infection with T.gondii may confer risk for mania.