Background: Rheumatoid arthritis (RA) is a long-lasting inflammatory disease characterized via synovial inflammation and joint destruction. Tumor necrosis factor-alpha and interleukin-6 are key mediators. Adalimumab is operative; a percentage of patients show inadequate response. C-reactive protein and erythrocyte sedimentation rate are widely used inflammatory markers, but limited ability to predict treatment response. Calprotectin has been projected as a biomarker of illness activity. Adipose tissue secretes pro-inflammatory cytokines and related to reduced response to TNF inhibitors. Objectives: To assess serum CRP and calprotectin ranks in RA patients cured with adalimumab and to evaluate their connotation with BMI and medical response. Methodology: A cross-sectional comparative study included 130 participants: 75 RA patients receiving adalimumab and 55 controls. Patients included 25 males and 50 females; mean age 47.57 ±10.68 (responders n = 35) and 46.40 ±8.76 (non-responders n = 40), classified according to European Alliance of Associations for Rheumatology criteria, using Disease Activity Score28 with Erythrocyte sedimentation rate. CRP and calprotectin were measured using Enzyme-Linked Immunosorbent Assay. Results: RA patients showed higher CRP and calprotectin levels paralleled to controls (p < 0.001). Calprotectin did not differ between responders and non-responders, while CRP was higher in non-responders (p < 0.001). BMI was positively correlated with calprotectin (r = 0.746) and CRP (r = 0.655) (p < 0.001). Conclusion: CRP and calprotectin are elevated in RA patients treated with adalimumab; Only CRP is associated with treatment response. Calprotectin reflects inflammatory burden, while obesity is related with augmented inflammatory indicators and may negatively influence outcomes.