Introduction Rheumatoid arthritis (RA) is a systemic autoimmune disease presented by inflammatory polyarthritis, affecting predominantly smaller joints such as hands and feet but can also affect large joints. Heat shock protein 70 (HSP70) is released from damaged cells after stress and has been found in the bloodstream of patients with RA. Aim To study the applicability of HSP70 serum levels as a diagnostic factor and a severity indicator in patients with RA Patients and methods The study included 59 patients with RA and 14 controls. Patients were classified according to disease activity score 28 into four groups: 10 patients in remission, 12 patients with low disease activity, 18 patients with moderate disease activity, and 19 patients with high disease activity. HSP70 and anti‑cyclic citrullinated peptide assessments were done by ELISA technique. Results Patients with RA had a higher HSP70 level than the control group (P < 0.001), irrespective of presence or absence of rheumatoid factor or anti‑citrullinated cyclic peptide. Next, diagnostic accuracy of the HSP70 in diagnosis of RA was evaluated (area under curve = 0.91). HSP70 had 89.8% sensitivity and 92.8% specificity in diagnosis of RA. In addition to diagnostic value, HSP70 can distinguish between high disease activity (76.67 ± 16.06 ng/ml) and mild (25.57 ± 7.39 ng/ml), moderate (35.17 ± 8.34 ng/ml), or remission phase (16.90 ± 4.06 ng/ml). Conclusion The study demonstrates an increase in the serum level of HSP70 in patients with RA in comparison with controls.