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Background: Progressive acute respiratory failure with Mycobacterium tuberculosis(TB) in immunocompetent individuals is rare, and if detected early, diagnosis and treatment dilemmas can be limited. We report here a unique case of respiratory failure due to tubercular spontaneous pneumomediastinum complicated by acute respiratory distress syndrome (ARDS). Case presentation: A 24-year-old male of low socioeconomic background presented with shortness of breath, dry cough, and fever for 7 days, which was accompanied by weight loss and a reduced appetite. The patient had tachypnea and hypoxemia (SpO2= 86%). The patient’s condition deteriorated (SpO2= 72% with 12 L min−1of O2delivered using a non-rebreather mask), and he was intubated using a lung-protective approach with a tidal volume of 350 mL (6 mL kg−1), positive end-expiratory pressure (PEEP) of 5 cm H2O, RR of 20 cycles/min, a flow rate of 35 L min−1, and FiO2of 0.6. High-resolution computer tomography of the thorax showed multilobar consolidation, pneumomediastinum, and extensive subcutaneous emphysema with left-sided pneumothorax. Subsequently, a left-sided tube thoracostomy was carried out. The PaO2/FiO2(P/F) ratio immediately after intubation was 130 and rose to 170 post-thoracostomy, which was suggestive of moderate ARDS. Bacterial and fungal colonies detected from the blood and endotracheal aspirate were normal. However, for the endotracheal aspirate, the cartridge-based nucleic acid amplification test (CBNAAT) detected TB with no rifampicin resistance. The patient was started on anti-tubercular therapy (ATT). Despite ATT, the patient developed circulatory shock and died after 4 days. Conclusions: In young patients with acute spontaneous pneumomediastinum and ARDS, TB infection should be considered during initial diagnostics. This consideration may lead to timely treatments and improved patient survival.