The effect of acute pre-surgery dexamethasone treatment on the inflammatory immune and endocrine responses to orthopaedic surgery was investigated. Whole blood samples were obtained before and 5 days after surgery for immune analysis, and serum was obtained before and 6 h, 3 days and 5 days after surgery for endocrine assessment. Dexamethasone did not affect the post-surgery granulocyte response, but inhibited the increase in monocyte count (an average increase of 38.5% was seen in the control group). Peak C-reactive protein concentration (3 days after surgery) was 51.4% lower in the dexamethasone group than in the control group. Dexamethasone had a major effect on cortisol concentrations and the cortisol:testosterone and cortisol:dehydroepiandrosterone ratios, but no effect on anabolic hormone concentrations. In conclusion, acute pre-surgery dexamethasone treatment may have beneficial effects in the post-surgery period, by limiting the extent of systemic inflammation and the cortisol response.