ABSTRACT: Mycobacteriosis, a chronic bacterial disease of fishes, is prevalent in adult striped bass from Chesapeake Bay (USA). Although environmental factors may play a role in disease expression, the interaction between the disease and environmental stress remains unexplored. We therefore examined the individual and interactive effects of elevated temperature, hypoxia, and mycobacteriosis on the metabolism of wild-caught adult striped bass from Chesapeake Bay using respirometry. Because the spleen is the primary target organ of mycobacteriosis in striped bass, we hypothesized that the disease interferes with the ability of fish to increase their hematocrit in the face of increasing oxygen demands. We determined standard metabolic rate (SMR), maximum metabolic rate under normoxia (MMR_N), critical oxygen saturation (S_crit), and MMR under hypoxia (3 mg O₂ l^-1: MMR_H) for healthy and visibly diseased fish (i.e. exhibiting skin lesions indicative of mycobacteriosis). Measurements were taken at a temperature within the preferred thermal range (20°C) and at an elevated temperature (28°C) considered stressful to striped bass. In addition, we calculated aerobic scope (AS_N = MMR_N - SMR, AS_H = MMR_H - SMR) and factorial scope (FS_N = MMR_N SMR^-1, FS_H = MMR_H SMR^-1). SMR increased with increasing temperature, and hypoxia reduced MMR, AS, and FS. Mycobacteriosis alone did not affect either MMR_N or MMR_H. However, elevated temperature affected the ability of diseased striped bass to tolerate hypoxia (S_crit). Overall, our data indicate that striped bass performance under hypoxia is impaired, and that elevated water temperatures, hypoxia, and severe mycobacteriosis together reduce aerobic scope more than any of these stressors acting alone. We conclude that the scope for activity of diseased striped bass in warm hypoxic waters is significantly compromised.