Prolonged high secretion of glucocorticoids normally reflects a state of chronic stress, which has been associated with an increase in disease susceptibility and reduction in Darwinian fitness. Here, we hypothesize that an increase in oxidative stress accounts for the detrimental effects of prolonged high secretion of glucocorticoids. We performed a meta-analysis on studies where physiological stress was induced by administration of glucocorticoids to evaluate the magnitude of their effects on oxidative stress. Glucocorticoids have a significant effect on oxidative stress (Pearson r = 0.552), although this effect depends on the duration of treatment, and is larger in long-term experiments. Importantly, there was a significant effect on tissue, with brain and heart being the most and the least susceptible to GC-induced oxidative stress, respectively. Furthermore, effect size was larger (1) in studies using both sexes compared to males only, (2) when corticosterone rather than dexamethasone was administered and (3) in juveniles than in adults. These effects were not confounded by species, biochemical biomarker, or whether wild or laboratory animals were studied. In conclusion, our meta-analysis suggests that GC-induced oxidative stress could be a further mechanism underlying increases in disease susceptibility and decreases in Darwinian fitness observed under chronic stress.