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Background: Muscle weakness is a part of the wasting syndrome associated with TB. Cytokines are candidates as the initial causative agents of the metabolic changes in TB. The objective of this study is to assess the peripheral and respiratory muscle strength in patients with TB and controls and relate these findings with leptin, IL‐6 and TNF‐α serum levels. Methods: Case–control study. Hospitalized patients with pulmonary TB and controls were included. Maximal voluntary handgrip strength (HS), maximal inspiratory pressure (MIP) and maximum expiratory pressure (MEP) were measured. Leptin, IL‐6 and TNF‐α dosage were performed. Results: We included 35 cases and 35 controls. Leptin was lower and TNF‐α levels were higher in TB patients than in controls (P < .0001 for both). Body mass index (BMI), HS, MIP and MEP were all significantly lower in cases than in controls (P < .0001). Lower leptin and higher TNF‐α levels are associated with malnutrition and reduced MIP, MEP and HS. Patients who reported fever and those with positive culture for Mycobacterium tuberculosis had higher serum levels of IL‐6. Conclusion: Peripheral and respiratory muscle strength and leptin levels were reduced in patients with active TB. Lower levels of leptin and higher levels of TNF‐α were associated with malnutrition and with reduced MIP, MEP and HS. [ABSTRACT FROM AUTHOR]