Objective: This study was conducted to investigate the immunological and clinical response to COVID-19 vaccination in rheumatoid arthritis (RA) patients receiving disease modifying antirheumatic drugs (DMARDs). Methods: A cross-sectional study was conducted among RA patients who received two doses of COVID-19 vaccine within 6 months to one year. Demographic information, comorbidities, vaccination details, and past COVID-19 infection details were collected. Hemoglobin (Hb), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and interleukin-6 (IL-6) levels were estimated. Disease Activity Score-28 (DAS-28) was calculated for RA patients. Anti-spike antibody (ASA) concentrations were measured, and compared with a healthy control population. Correlations of ASA with age, sex, disease parameters, medication use, and comorbidities were assessed. Results: A total of 103 RA patients and 185 controls were included in the study. RA patients had higher mean age, lower mean Hb, higher ESR, and elevated IL-6 levels. Both groups showed positive results for anti-spike antibodies, with a higher percentage in controls. Among RA patients majority had low DAS-28 score. The number of DMARDs used showed a negative correlation with antibody levels. There was a slight positive correlation between ASA concentration and DAS-28 score. Comorbidities did not significantly influence antibody concentration. No significant differences were found in antibody levels based on the type of COVID-19 vaccine or previous COVID-19 infection or booster dose vaccination among RA patients. Conclusion The study revealed that RA patients showed a reduced antibody response following COVID-19 vaccination compared to the control group and potentially influenced by immunosuppressive treatments and disease-related factors.