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Abstract Background Blood dyscrasias are common in patients with rheumatic diseases, as bone marrow and blood cells can be targets for autoimmune processes. This in addition to the potentially adverse effect of the disease-modifying anti-rheumatic drugs used for the treatment of inflammatory arthritis as in psoriatic arthritis (PsA) and ankylosing spondylitis (AS) on blood counts. Aim of this study The aim of this study is to analyze the effect of biologic therapy on complete blood cell parameters, derived ratios, and cell volume indices in Egyptian patients with ankylosing spondylitis and psoriatic arthritis. Results One hundred and twenty Egyptian patients had been included, 60 have ankylosing spondylitis (AS) and 60 have psoriatic arthritis (PSA). On comparing the blood indices between the biologics and non-biologics groups of PSA patients, there was a statistically highly significant reduction in red cell distribution width (RDW%) at the biologics group than non-biologics (p < 0.006), where there was a statistically highly significant increase in Hb (hemoglobin)/RDW ratio and Hb/platelets ratio at the biologics group than non-biologics (p < 0.005). Conclusion As a result, biologic drugs used in rheumatology practice may have some effects on hematological parameters. In our study, no major negative effects on hematological parameters were observed in patients with AS and PsA who received Secukinumab, Adalimumab-atto, or Golimumab biologic therapy. However, the changes in the hematological indices correlates with their potent anti-inflammatory action in rheumatic patients.