Objective Species‐related differences in the prevalence, manifestation, and outcome of neonatal illness may impact management practices of neonatal intensive care. The study aimed to elucidate similarities between disease manifestations and mortality risks of critically ill (CI) neonatal crias and foals admitted to the same referral center. Design A comparative, retrospective cohort evaluation of two species (camelid and equine). Setting The study was conducted in a University hospital. Animals Two hundred and forty‐six CI neonatal crias (January 1999 to May 2016) and 356 neonatal foals (February 2001 to May 2016) under 4‐week‐old were admitted to a university hospital. Intervention All data are presented descriptively and compared between groups using univariate and multivariate analyses. Measurements and Main Results Female crias (142/246, 57.7%) were significantly overrepresented in comparison to fillies (132/352, 37.5%). Congenital defects and transfer failure of passive immunity were more often observed in neonatal crias, while colic, diarrhea, patent urachus, septic arthritis, and omphalitis were significantly more common in CI foals. Overall survival to discharge (excluding fatal congenital defects) was comparable between crias (174/224; 77.8%) and foals (287/347, 82.1%), while crias (26/48; 54.2%) were more likely than foals (21/60; 35%) to die naturally than undergo euthanasia. Lower respiratory disease and indications for oxygen or IV glucose support increased mortality in the multivariate outcome models of both species. Species‐specific adaptations of pediatric diagnostic criteria for sepsis were significantly associated with mortality in the multivariate analysis of patients with complete hematological datasets. However, the diagnosis of systemic inflammatory response syndrome (SIRS) did not retain statistical significance as an independent outcome predictor. Conclusions Lower respiratory disease and oxygen or glucose dysregulation increased mortality irrespective of species. However, despite species‐specific differences in disease prevalence, the success of intensive care management was comparable.