It is well established that stress and the attendant rise in glucocorticoids (GCs) results in immune suppression. Indeed, the anti-inflammatory properties of GCs have been exploited therapeutically for decades. However, pharmacological treatment with GCs often recapitulates a chronic stress scenario, and, in contrast, it has been shown that exposure to an acute stressor can augment both the innate and adaptive immune responses. While this bidirectional effect of stress has been described, little is known about the molecular mechanisms involved. Cortisol, the primary GC in humans, signals through two corticosteroid receptors, the low-affinity glucocorticoid receptor (GR), which mediates anti-inflammatory actions, and the high-affinity mineralocorticoid receptor (MR), described to modulate pro-inflammatory actions. Here we tested the hypothesis that MR would promote the immune-enhancing effects of acute stress while chronic activation of GR would lead to immune suppression. To study this, we used transgenic zebrafish larvae which allowed for the real-time visualization of fluorescently labeled leukocytes (macrophages and neutrophils). We first observed that macrophages rapidly redistributed towards the dermis post-stress and that this was dependent on both GR and MR’s modulation of the macrophage CXC chemokine receptor type 4 (cxcr4b). To determine whether this redistribution resulted in an enhanced response to inflammation, we amputated the tail fin of the larvae and quantified the number of leukocytes localized at the wound site. While chronic cortisol treatment reduced the number of leukocytes localized to the wound, acutely stressed larvae increased macrophage recruitment 2-fold, independent of redistribution. This increase in macrophage recruitment was due to the modulation of macrophage CXC chemokine receptor 3 (cxcr3.2) expression by GR, independent of MR. Taken together our data suggests the immunological role of GR is more complex than initially thought, where acute activation enhances the immune response and chronic activation leads to immune suppression.