Infection with systemic Isospora species (systemic isosporiasis [SI]) is common in passerine birds and may cause substantial mortality in zoological collections. Ten years of postmortem records of 26 species of captive, nonnative passerine birds maintained at the Zoological Society of London, London Zoo, plus seven free-ranging species found dead within the zoo, were reviewed to assess cause of death and occurrence of SI (presence of merozoites in tissue impression smears and/or polymerase chain reaction [PCR] testing for Isospora DNA). The records of 287 juveniles and adults were reviewed, of which 161 had SI test results. The most common cause of death was physical (trauma, predation, drowning, and hypothermia), diagnosed in 39.0% of cases. Virulent SI was considered the cause of death in only nine individuals from five species (3.1% of all cases, 5.6% of tested birds). However, merozoites were recorded in 36.0% of the 150 individuals examined cytologically (representing 18 of the 33 species), while 45.3% of 53 spleen samples (14 species) were positive for Isospora DNA. Test agreement for the 42 birds tested by both methods was 69.0%. Assuming that the PCR result was correct in these, 37.9% of the 161 birds (21 species) were positive for SI at the time of death. These figures might underestimate prevalence because of poor DNA preservation and low numbers of individuals of some species tested. Eight new 28S rDNA sequences and 12 new internal transcriber spacer 1/2 sequences were amplified. Sequences from individuals of the same host species clustered together, suggesting a single Isospora species, and there was no evidence of overlap among hosts. These results confirm that systemic infection with Isospora species in zoo passerines is generally of low pathogenicity and most likely coevolved with their hosts. Severe disease may occur, however, with overwhelming exposure, secondary to immunosuppression, or following coinfection with another pathogen.