Introduction: Interpreting the interactions between M. tuberculosis and the host innate and adaptive immune defense mechanisms is mandatory for understanding the pathogenesis of active pulmonary TB (APTB). The aim was to describe the distribution of mononuclear cells in APTB and their relation to disease severity. Methodology: A case-control study of peripheral blood CD4+ T cells, CD8+ T cells, B-lymphocytes, NK cells, T regulatory lymphocytes (Tregs) and monocytes by flow cytometry. The patients had clinical presentations of APTB, positive tuberculin skin tests, acid-fast bacilli smears and sputum cultures using BACTEC 960. Results: There was a significant decrease in the haemoglobin level and the absolute lymphocytic count (p < 0.01), while both the neutrophil count and erythrocyte sedimentation rate showed significant increase in the APTB patients compared to HC with p-values < 0.001 and < 0.0001 respectively. Both the CD4+/CD8+ ratio and the percentages of CD3−CD19+ cells were significantly lower in APTB patients (p = 0.03 and p = 0.005 respectively). The percentages of CD4+, CD8+, CD3−CD19+, CD14+, and CD3−CD (16+56)+ cells showed no significant differences, when comparing either disease severity groups, or cavitated and non-cavitated groups of APTB patients. There was significant increase in the CD4+25+ lymphocytes in the advanced APTB patients than in the mild disease group (p < 0.05). Conclusions: B-lymphocytes and CD4/CD8 ratios were significantly lower in the APTB patients than controls with no association with disease severity. CD4+ CD25+hi Tregs were significantly higher in the advanced versus mild groups.