Monocytes from tuberculosis patients exhibit functional and phenotypical alterations compared with healthy controls. To determine whether these discrepancies can be explained by changes in monocyte subsets, the expression of CD14 and CD16 was evaluated in tuberculosis patients and healthy controls; additionally, some markers related to the mononuclear phagocytes maturation, differentiation and function, such as CD1a, CD1c, CD11b, CD11c, CD13, CD33, CD36, CD40, CD64, CD68, CD80, CD83, CD86, HLA-DR, CCR2, CCR5, and non-specific esterases (NSE) were determined in monocyte subsets. Patients had increased percentage of circulating CD14^HiCD16⁺ and CD14^LoCD16⁺ monocytes. The percentage of monocytes expressing CD11b, CD36, CD64, CD68, CD80, CD86, CCR2 and NSE was lower in CD14^HiCD16⁺ and CD14^LoCD16⁺ cells than in CD14^HiCD16⁻ monocytes. M. tuberculosis infected CD16⁺ monocytes produced more TNF-⍺ and less IL-10 than CD16⁻ cells at 6 h post-infection. Isolated CD16⁺ monocytes spontaneously underwent apoptosis during differentiation into macrophages; in contrast to CD16⁻ monocytes that became differentiated into monocyte-derived macrophages (MDM) with a minimal induction of cell death. In addition, there were more Annexin V and propidium iodide positive monocytes in the CD16⁺ subset infected with live M. tuberculosis at 24 h than CD16⁻ monocytes. Under the culture conditions established for this study, the monocyte subsets did not differentiate into dendritic cells. These results show that tuberculosis patients have an augmented frequency of CD16⁺ circulating monocytes which are more prone to produce TNF-⍺ and to undergo cell death in response to M. tuberculosis infection.