Background: Serum calprotectin (CLP) has an important role in regulating innate and adaptive immune response. Its evaluation in rheumatic diseases can offer better outcomes for controlling and predicting disease activity  Aim of the work: This work aimed at assessing serum CLP in patients with rheumatic diseases and estimating its relation with clinical, laboratory and musculoskeletal ultrasound. Patients and methods: Our randomized study included 60 patients of both sexes, with rheumatoid arthritis (RA), psoriatic arthritis (PSA) and ankylosing spondylitis (AS) and a control group of 20 apparently healthy volunteers . All patients were subjected to serum CLP evaluation besides clinical and musculoskeletal ultrasound assessment. Results: Serum CLP was significantly higher in all patients with significant difference between patients and control group. No significant correlation was detected between calprotectin and disease activity parameters other than significant negative correlations with inflammatory markers in RA & AS and positive correlation with DAPSA score. Conclusions: CLP serum levels were particularly high in RA, PSA and AS and can be used to differentiate these autoimmune diseases. CLP offers a good alternative when CRP is negative.