Background and Objectives: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a viral disease that is spreading worldwide and became a pandemic. Although most of the time, the symptoms of the infection are flu like, a percentage of patients develop severe forms, along with severe complications. Many of them are known among front-line health workers, but the number of uncommon presentations and complications has increased. This case report aims to alert healthcare workers on less common forms of presentation, and to introduce this differential diagnosis in the evaluation of patients with COVID-19, given the increasing occurrence of pneumothorax in patients who are not mechanical ventilated. Case presentation: A 57-year-old female patient came to the Emergency Department (ED) by ambulance, with acute respiratory failure. She had SpO2 = 43% on room air at home, and 86% on admission in ED after oxygen delivery (on a reservoir mask). SARS-CoV-2 infection was suspected based on symptoms that started three days ago (fever, dry cough, dyspnea, and fatigability). Blood was taken for lab tests, pharyngeal and nasal swabs for the reverse transcription–PCR (RT-PCR) test, and native computed tomography (CT) was scheduled. The thoracic CT scan showed massive right pneumothorax, partially collapsed lung, multiple bilateral lung infiltrates with a ground glass aspect and the RT-PCR test came back positive for SARS-CoV-2 infection. Despite the prompt diagnosis and treatment of pneumothorax (thoracostomy was performed and the drain tube was placed), the patient died after a long hospitalization in the intensive care unit. Conclusion: Secondary spontaneous pneumothorax (SSP), as a complication in severe forms of COVID-19 pneumonia, especially in female patients without risk factors is rare, and early diagnosis and treatment are essential for increasing the survival chances of these patients.