Cortisol, and other glucocorticoids, are routinely used as markers of physiological stress in wildlife. Typically, stress activates the hypothalamic–pituitary–adrenal (HPA) axis, with adrenocorticotropic hormone (ACTH) signaling the adrenal glands to release cortisol. Nevertheless, recent anecdotes in captive Coquerel's sifakas (Propithecus coquereli), strepsirrhine primates that are difficult to maintain under human care, may challenge the assumption that physiological stress universally increases circulating cortisol. Here, the authors ask if low circulating cortisol and minimal response to adrenal stimulation might be hallmarks of outwardly healthy sifakas in captivity. Comparative ACTH stimulation or control tests were performed in 10 Coquerel's sifakas and six ring-tailed lemurs (Lemur catta) at the Duke Lemur Center (DLC). At baseline, sifakas had average cortisol concentrations of just 0.67 µg/dl, whereas those of ring-tailed lemurs averaged 12.53 µg/dl. Stressful pre-experiment procedures, including kenneling and handling, activated the HPA axis in ring-tailed lemurs, masking further cortisol release from ACTH administration; however, neither these procedures nor exogenous ACTH raised cortisol concentrations in sifakas. Additionally, cortisol in dozens of serum samples from DLC sifakas banked over 17 yr was assayed. Across samples, cortisol concentrations averaged just 0.49 µg/dl and did not vary by animal sex, age, or housing condition. Comparable samples from two individual sifakas in sepsis at the end of life (4.28 and 21.88 µg/dl) indicate that the assay does capture meaningful variation in cortisol in captive sifakas, although robust biological validation is needed. Currently there is a lack of comparative data from wild Coquerel's sifakas that might determine if these unusual endocrine patterns are characteristic of the species or a function of captivity. If the latter, chronic stress in captivity could lead to a downregulated HPA axis, with persistent hypocortisolism perhaps contributing to the Coquerel's sifaka's susceptibility to infection under human management.