Infection with Toxoplasma gondii is a rare but often fatal complication in hematopoietic stem cell transplantation (HSCT) recipients. Most cases have been reported in allogeneic (allo-) HSCT recipients, with only narrative reports following autologous HSCT (ASCT). We report the case of a 58-year-old Caucasian male presenting with toxoplasma encephalitis following tandem ASCT for myeloma and successfully treated with diagnosis by polymerase chain reaction analysis of cerebrospinal fluid. He was treated with sulfadiazine and pyrimethamine (with leucovorin) followed by pyrimethamine and atovaquone as secondary prophylaxis while receiving subsequent therapy for progressive multiple myeloma. Toxoplasmosis is a potential complication in allo-HSCT as well as ASCT recipients and should be considered in any post-HSCT patient with neurological dysfunction. Rapid diagnosis and immediate antimicrobial treatment are essential to avoid morbidity and mortality.