Background Calprotectin is a protein released during the activation and turnover of leukocytes. It can be used as a biomarker of inflammatory diseases such as rheumatoid arthritis (RA). Aim The current study aimed to measure the serum level of calprotectin in RA patients, recently diagnosed and after initiation of treatment, to determine its association with clinical disease, synovial inflammation determined by Ultrasound (US), and its relation to therapy when compared with other inflammatory markers. Patients and methods A total of 32 patients with recent RA and 20 healthy individuals were assessed for serum calprotectin level (enzyme-linked immunosorbent assay). C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were also measured in patients who were reassessed 4 months after initiation of therapy. Disease activity was evaluated by the disease activity score of 28 joints (DAS28), and US assessment was performed. Results The mean level of serum calprotectin was significantly higher (P