Stress-induced inhibition of innate immune activity has been observed in a variety of wild birds and may increase chances of infection because this activity constitutes the first line of defense against pathogens. We previously reported that the transient elevation of plasma corticosterone (CORT; the primary avian glucocorticoid) that occurs during stress is necessary for stress-induced suppression of natural antibody-mediated, complement-mediated, and bactericidal activity. Here, we further investigated the regulatory role of CORT during this suppression. To this end, we treated House Sparrows (Passer domesticus) with mitotane to block endogenous CORT production, administered CORT at one of three doses (HI: 1.34 mg/kg; LO: 1.00 mg/kg; CON: vehicle), and assessed natural antibody-mediated, complement-mediated, and bactericidal activity during acute stress induced by handling and restraint. Mitotane administration eliminated the endogenous plasma CORT increase that normally takes place during stress, and corticosterone treatment increased plasma CORT to levels similar to those measured in intact birds during acute stress. As predicted, mitotane-treated birds receiving CON injections did not exhibit stress-induced suppression of complement-mediated and bactericidal activity, and CORT administration at both LO and HI doses restored this suppression. Contrary to expectations, mitotane-treated birds receiving CON injections demonstrated stress-induced suppression of natural antibody-mediated activity. Furthermore, CORT administration did not influence this parameter. These results suggest that stress inhibits innate immune activity through both CORT-dependent and CORT-independent mechanisms, but the contribution of these mechanisms can vary. This variation may result from effects of environmental factors, the identity and role of which warrant further research.