Introduction: The use of remdesivir is not recommended in patients with end-stage renal disease (ESRD) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection unless potential advantage offset disadvantage due to limited safety data. Our objective was to assess the safety of remdesivir in patients with end-stage renal failure and evaluate the outcome of this vulnerable group. Methodology: We carried out a retrospective observational study in dialysis-dependent ESRD patients with SARS-CoV-2 infection who received a standard 5-day course of remdesivir (powder form) from June 2020 to December 2020. Oxygen requirement, hemogram, inflammatory markers, and liver function tests before and after remdesivir treatment were compared. Result: We found thirty-nine such patients with mean age of patients 58.79 ± 12.13 years. Diabetes mellitus, hypertension, and cardiac diseases were present in 58.97, 87.17, and 23.07% of patients, respectively. Mean oxygen saturation on admission was 85.41% (±7.73). There were no events of hepatotoxicity, altered behavior, or infusion reaction. There was statistically significant improvement in total leukocyte count, absolute lymphocyte counts, and C-reactive protein (p value <0.001, 0.01, and 0.02, respectively) post remdesivir treatment. A total of 60% of patients had improved oxygenation while 13% of patients had no change in oxygen requirement after completion of remdesivir course. Mortality in our study was 28.21%. We did not find any significant benefit of early remdesivir administration (3–6 days of illness) on mortality or days of hospitalization. Conclusion: The use of remdesivir in end-stage kidney disease is safe. Improvement in oxygenation was significant when baseline oxygen requirement was less. It requires prospective controlled trials with larger population to assess its impact on mortality.