Background: Malignant ischemic stroke is a known cerebrovascular complication in patients with SARS-CoV-2 infection, and decompressive craniectomy has been proposed as a treatment option. However, there is limited data available on the outcomes of patients with malignant stroke and concurrent SARS-CoV-2 infection. This study aimed to investigate whether decompressive craniectomy is beneficial for patients with malignant stroke and SARS-CoV-2 infection. Methods: This case-control study was conducted between March 2020 and December 2021, involving patients diagnosed with malignant stroke who underwent decompressive craniectomy. A total of 52 patients were included and divided into two groups: Group 1 consisted of patients with malignant ischemic stroke and concurrent SARS-CoV-2 infection (n = 20), while Group 2 comprised patients with malignant ischemic stroke without SARS-CoV-2 infection (n = 32). Medical data were collected for analysis. Results: The data analysis included variables such as diagnosis of COVID-19 and clinical outcome of death. Statistical tests, including the Chi-squared test with Yates's correction (p = 0.9094), Fischer's Exact Test (p = 0.7708), Coefficient φ (0.0568), and Odds Ratio (1.273, 95% CI: 0.4332 -4.343), were conducted using a contingency table. The results showed no significant association between SARS-CoV-2 infection and the clinical outcome of death. Conclusion: The findings indicate that patients with SARS-CoV-2 infection benefit from decompressive craniectomy for the treatment of malignant stroke to the same extent as patients without viral infection. This study provides valuable insights into the efficacy in patients with malignant stroke and SARS-CoV-2 infection. Further research is warranted to confirm these findings and explore additional factors that may influence patient outcomes in this context.