Introduction: Pneumothorax (PTX) and/or pneumomediastinum (PMD) are rare complications of Coronavirus Disease-2019 (COVID-19) and are linked to high mortality. Incidence rates vary between 0.56-2.01% in the reported literature. With clinical examination being hampered in the current pandemic setting, there is a delay in the diagnosis. There is a need to identify and establish potential predictive factors, that may aid in identifying patients with a high-risk of developing PTX and/or PMD. Aim: To identify potential risk factors and thus, explore their association with PTX and/or PMD among patients with COVID-19. Materials and Methods: A retrospective case-control study was conducted at MS Ramaiah Medical College and Hospital, Bangalore, South India over a six-month period. A total of 130 patients diagnosed with COVID-19 were recruited in a 1:3 ratio as cases and controls respectively. Cases were patients, diagnosed radiologically with PTX and/or PMD, and controls were, matched individuals without PTX and/or PMD. Patient’s clinical and laboratory parameters (complete blood count, renal and liver function tests, serum levels of inflammatory markers such as C-reactive protein (CRP), lactate dehydrogenase (LDH), and D-Dimer were tested for potential association with PTX and/or PMD. Student’s t-test, Chi-square test, multivariate and univariate logistic regression analysis were performed. Results: During the study period, there was a total of 3,251 COVID-19 admissions at the centre with 976 patients requiring Intensive Care Unit (ICU) admission. The overall incidence of PTX and/or PMD during the study period was (31/3251) 0.95%. The previous history of COVID-19, non vaccination with COVID-19 vaccine, cough as a predominant symptom, high values of baseline CRP, total bilirubin, Aspartate Transaminase (AST), and total leukocyte counts had a positive association. In-hospital mortality (54.8% vs 33.30%) and mortality 28 days (35.7% vs 7.6%) following discharge, were higher among those with PTX and/or PMD. Conclusion: Patients with a history of previous infection with COVID-19, non vaccination /incomplete-vaccination with COVID-19 vaccines, and patients with increasing total leukocyte counts and AST levels, high baseline total serum bilirubin were at increased risk of a detrimental clinical course and may indicate, the possibility of development of PTX and/or PMD in COVID-19 disease.