Pseudoloma neurophilia (Microsporidia) is a common disease of zebrafish, Danio rerio, including those used as research models. We conducted a study comprised of four separate experiments to determine the effects of husbandry stress on pre-existing and experimental Pseudoloma infections and the subsequent effects on survival, infection onset and intensity, fish growth and reproduction. In fish (AB strain) with pre-existing infections, stress or feeding cortisol significantly increased mortality over 7 wk compared to no stress or cortisol treatment. In contrast, no mortality was observed in fish (TL strain) experimentally-exposed to Pseudoloma over 10 wk. A third experiment involved experimental exposure of AB fish to Pseudoloma and exposure to crowding and handling stressors. No mortality was associated with Pseudoloma regardless of stress treatment over a 20 wk period. However, the onset of infection occurred sooner in stress-treated fish. Stress significantly increased the mean intensity of infection (described as xenoma area/spinal cord area in histological sections) at wk 20 PE (post-exposure). In fish with pre-existing infections, myositis was significantly greater in stressed and cortisol-treated fish than those not stressed. With experimental exposure of AB fish, stressed and infected groups weighed significantly less than the control group at wk 20 PE. Regarding fecundity, the number of larvae hatched at 5 days post fertilization was negatively associated with mean infection intensity among Pseudoloma-infected and stressed AB fish. These experiments are the first to show empirically that Pseudoloma can be associated with reduced weight and fecundity, and that stress can exacerbate the severity of the infection.