The Southern African Foundation for the Conservation of Coastal Birds (Cape Town, South Africa) regularly receives African Penguins (Spheniscus demersus) for rehabilitation. The impact of life history and clinical parameters at admission of 3,975 chicks, 1,687 blues (chicks without downy plumage that are about to fledge or have recently fledged), and 850 fledged juveniles admitted over a 12 yr period (2002–13) were assessed in relation to rehabilitation outcomes using multivariate analysis. Younger chicks were more likely to die during rehabilitation compared with older chicks, and chicks admitted because they had been abandoned by their parents were more likely to die than those admitted preemptively (chicks that were removed when rangers considered their nests were in high-risk areas). Blues admitted because of injury and juveniles admitted because of debilitation, injury, and molt were more likely to die or be euthanized relative to the reference category oiling. Plasmodium infection contributed to natural death for all age groups and to the decision to euthanize chicks, whereas Borrelia infection contributed to both natural death and the decision to euthanize blues. Babesia infection was associated with decreased odds of euthanasia among juveniles. Low hematocrit at admission contributed to natural death of chicks and blues and euthanasia of blues. Low total plasma protein, on the other hand, contributed to natural death in chicks, blues, and juveniles, whereas high total plasma protein had a protective effect against natural death in chicks. These results indicate a need to focus on prevention and early intervention among compromised immature penguins in order to increase the rehabilitation success for this endangered species.