Dexamethasone is commonly used in the clinic to treat auto-immune disease and inflammation. Despite being relatively safe at a low dose, high-dose dexamethasone causes (severe) side effects such as obesity and insulin resistance in the majority of patients. Dexamethasone has a high affinity for the glucocorticoid receptor (GR) and completely suppresses endogenous GC production. Since dexamethasone only has a very low affinity for the mineralocorticoid receptor (MR), (side) effects of dexamethasone may be the result of GR hyperactivation as well as MR hypoactivation. We therefore hypothesized that reactivation of MR, via co-administration of a low dose of corticosterone, can reduce part of the metabolic (side) effects of dexamethasone treatment. 8-week old male mice received fructose water and a high-fat diet (HFD) mixed with dexamethasone or vehicle, next to subcutaneously implanted vehicle or low-dose corticosterone pellets. Dexamethasone strongly reduced fat mass gain, while corticosterone add-on fully normalized this. Dexamethasone induced hyperglycaemia and hyperinsulinemia, which was aggravated by corticosterone add-on. In subcutaneous white adipose tissue (WAT), dexamethasone decreased adipocyte size and increased expression of rate-limiting lipolysis enzyme Atgl, while corticosterone add-on prevented both effects. In brown adipose tissue (BAT), dexamethasone increased the uptake of lipoprotein-derived triglycerides, irrespective of corticosterone. Dexamethasone additionally upregulated expression of BAT identity markers genes, lipid transporters and Atgl, which was suppressed by corticosterone add-on. Aldosterone add-on during dexamethasone treatment did not influence the dexamethasone-induced effects on body weight, fat mass, plasma insulin levels and glucocorticoid target gene expression. In conclusion, corticosterone add-on treatment prevents some, and enhances other metabolic effects of dexamethasone. While the exact role of MR remains inconclusive, this study suggests that corticosterone suppression by dexamethasone is relevant to its effects.