Background: Rheumatoid arthritis (RA) is an inflammatory form of arthritis that affects around 1% of adults worldwide. Symmetric polyarticular synovial inflammation is its defining feature. Nephroblastoma overexpressed protein (CCN3) proteins are important mediators of organogenesis and inflammation; CCN3 was found in synovial tissues of patients with RA and Osteoarthritis. Objective:  Consequently, goal of this research was to establish significance of serum CCN3 levels in RA patients and their relationship to disorder activity and severity. Methods: This case control investigation was performed on 50 subjects who were allocated into two groups; patient group: thirty patients with RA and control group: twenty healthy volunteers with ages and sexes that are matched. All patients were exposed to rheumatological and systemic examinations, and assessment of RA activity and X-ray on both hands and feet. Results: RA patients had significantly greater levels of serum CCN3. Serum CCN3 levels and disorder activity in RA patients showed a positive, statistically significant connection.  There were significant positive correlations between CCN3 concentration and length of morning stiffness, number of tender and swollen joints, Visual Analog Scale, Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein(CRP), Disease Activity Score (DAS28), Rheumatoid Factor (RF), Anti cyclic Citrullinated peptid(Anti CCp), erosion score and joint space narrowing. Conclusions: Serum concentration of CCN3 was substantially higher in RA patients contrasted to controls.  This level in these patients was positively connected with the severity and length of the disorder. With bone degradation, joint degeneration, and diminished functional status in RA patients, the serum CCN3 level was strongly associated.