20 patients with Kellgren-Lawrence grade II-III knee osteoarthritis were randomized to a single intraarticular injection of either N-acetyl cysteine (NAC; 300mg/3mL) or hyaluronic acid (HA; 24mg/3mL). Patients were assessed for clinical scores, serum C-reactive protein level, and synovial fluid biomarkers before and 6 weeks after injection. Clinical results demonstrated no significant differences between groups for improvement in either visual analog pain scale scores or Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. In addition, reduction in serum C-reactive protein after 6 weeks did not significantly differ between groups. One synovial biomarker was observed to significantly differ between groups; reduction in total oxidant status after 6 weeks was greater in the group administered the NAC injection compared to HA injection.