It is well established that stress and the attendant rise in glucocorticoids (GCs) results in immune suppression. However, recent evidence suggests that acute stressors can augment innate and adaptive immune responses, altering both the location and responsivity of leukocytes. Leukocytes, such as macrophages, are highly responsive to GCs due to the expression of the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) in these cells, yet little is known regarding the immunological significance of acute stress on macrophage distribution. Here we tested the hypothesis that upon acute stress, macrophages would relocate to the periphery in order to increase barrier immunity. To study this, we used transgenic zebrafish harbouring fluorescently tagged macrophages, allowing for real-time visualization of the immune response to stress. 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 (Cxcr4). Indeed, mutagenesis of a key glucocorticoid response element (GRE) in the promoter region of cxcr4a completely abolished stress-induced macrophage redistribution. We next determined that the reason for macrophage redistribution post-stress was the production of Cxcl12a, a ligand for Cxcr4, by melanocytes. Finally, to confirm the immunological significance of macrophage redistribution we added a fluorescent, soluble antigen to test whether stress increased barrier immunity at the skin. Here we observed a marked increase in antigen uptake in macrophages exposed to acute stress. Taken together, our data suggests that stress-induced macrophage redistribution towards the dermis results in an increased barrier immunity, and that this may be part of a larger programme of acute stress-induced immune enhancement.