Pallas' cat [Otocolobus (Felis) manul] experiences a high mortality rate from toxoplasmosis. During the period 2006–2016, the overall mortality rate for this species from all causes during the first year of life was 71.59% in European Association of Zoos and Aquaria institutions, with the most significant infectious cause from systemic toxoplasmosis (20.6%) as confirmed by postmortem examination and histopathology. Clindamycin was used starting in 2014 in two collections that had previously experienced 100% mortality rates by toxoplasmosis in kittens less than one year of age, covering key Toxoplasma gondii exposure periods for kittens (n = 17) as a prophylactic measure. This protocol resulted in a 67.03% (95% confidence interval 41.76–78.61%) reduction in the first year mortality rate over a two-year period to 5.88% in those animals treated.