BACKGROUND AND OBJECTIVE: Prospective studies of children with septic arthritis report that adding dexamethasone to antibiotic therapy contributes significantly to clinical and laboratory improvement. This study sought to evaluate the effect of this regimen outside of a randomized controlled trial. METHODS: The sample consisted of children with septic arthritis hospitalized at a tertiary pediatric medical center in 2008 to 2013. Disease course and outcome were compared between children treated with antibiotics alone or with adjuvant dexamethasone, according to the admitting department policy. RESULTS: The cohort included 116 patients, 90 treated with antibiotics alone and 26 treated with antibiotics+dexamethasone. The groups were similar for age, symptom duration before hospitalization, body temperature, acute-phase reactant levels, and rate of positive fluid cultures (21.6% total). Compared with monotherapy, antibiotics+dexamethasone treatment was associated with a shorter duration of fever (mean 2.3 vs 3.9 days, P = .002), more rapid clinical improvement (mean 6.3 vs 10.0 days to no pain/limitation, P < .001), more rapid decrease in C-reactive protein level to <1 mg/dL (mean 5.3 vs 8.4 days, P = .002), shorter duration of parenteral antibiotic treatment (mean 7.1 vs 11.4 days, P < .001), and shorter hospital stay (mean 8.0 vs 10.7 days, P = .004). Recurrent symptoms of fever and joint pain occurred in 4 patients in the antibiotics+dexamethasone group after completion of the steroid course. CONCLUSIONS: Children with septic arthritis treated early with a short course of adjuvant dexamethasone show earlier improvement in clinical and laboratory parameters than children treated with antibiotics alone.