© 2022 Sociedade Portuguesa de PneumologiaBackground: Substance use disorder (SUD) causes conditions such as cognitive and behavioral disorders, anxiety, depression, and social isolation it also causes acute airway inflammation by affecting airway bronchial dynamics. The current study aimed to investigate the lung function, respiratory muscle strength, and exercise capacity in patients with SUD. Methods: One hundred-eighty three patients with SUD, a total of 119 healthy controls, 54 of whom were cigarette smokers and 65 of whom were non-smokers were included in the study. Spirometric tests, respiratory muscle strength (MIP and MEP), and the 6-Minute Walk Test (6-MWT) were assessed. The III National Health and Nutrition Examination Survey were used to evaluate respiratory symptoms in patients with SUD and cigarette smokers. Results: 86.3% of the SUD patients included in the study were using heroin, 9.2% were cannabis, and 5.5% were spice. The most common symptom in both SUD patients and cigarette smokers was shortness of breath, wheezing, and sputum production. After post-hoc tests, the FVC (p = 0.002), FVC (%predicted) (p < 0.0001), FEV1 (p = 0.002), FEV1 (%predicted) (p < 0.0001), FEV1/FVC (%) (p < 0.0001), PEF (p < 0.0001) and FEF%25-75 (p < 0.0001) lung function parameters were significantly lower in SUD patients than non-smokers. In addition, it was found that MIP (p < 0.0001), MIP (%predicted) (p < 0.0001), MEP (p < 0.0001), and MEP (%predicted) (p < 0.0001) values of SUD patients were significantly lower than non-smokers. Conclusion: The study findings indicate that substance use has an effect on lung functions and the most commonly reported symptoms are shortness of breath, wheezing, and sputum production. In addition, respiratory muscle strength and exercise capacity were decreased in SUD patients compared to non-smokers.