In bacterial bone infections, excessively formed oxidants may result in local and systemic oxidative stress. Vitamin C is the major extracellular nonenzymatic antioxidant, also implicated in bone cells metabolism and viability. The physiological functions of vitamin C largely depend on its redox status. We sequentially assessed oxidative stress markers, hydroperoxides and malondialdehyde (MDA), total antioxidant activity (AOA), total vitamin C, ascorbic acid (Asc), and oxidized/reduced vitamin C ratio in 137 patients with acute osteomyelitis (OM). Compared to 52 healthy controls, in OM group baseline serum hydroperoxides, MDA and oxidized/reduced vitamin C ratio were higher whilst Asc and AOA were lower (P < 0.05, resp.). On the other side, total vitamin C levels in patients and controls were similar (P > 0.05), thereby suggesting a relative rather than absolute vitamin C deficiency in OM. During the follow-up, oxidative stress markers, AOA, and oxidizedreduced vitamin C ratio were gradually returned to normal, while there was no apparent change of total vitamin C concentrations. Persistently high values of oxidized/reduced vitamin C ratio and serum MDA were found in subacute OM. In conclusion, acute OM was associated with enhanced systemic oxidative stress and the shift of vitamin C redox status towards oxidized forms.