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Background With the looming threat of recurrent waves of coronavirus disease-2019 (COVID-19) in the presence of mutated strains, it is of paramount importance to understand the demographic and clinical attributes of COVID-19 related mortalities in each pandemic wave. This could help policy makers, public health experts, and clinicians to better plan preventive and management strategies to curb COVID-19 related mortality. Materials and methods This was a hospital record-based, retrospective cross-sectional descriptive study, at a tertiary care hospital in Rishikesh, India. The study included all deceased patients between March 2020 and January 2021 (first wave) who had tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcription polymerase chain reaction (RT-PCR) and were hospitalized. The study was done to describe demography, clinical presentation, laboratory parameters, treatment given, and associated complications of all COVID-19 deaths. Result Out of 424 mortalities, 298 (70.38%) were males and 126 (29.62%) were females. Mean age of patients was 55.85 ± 16.24 years, out of which 19.5% were less than 45 years old, 33.6% were 45–60 years old, and 41.8% were more than 60 years old. Comorbidity in the form of type II diabetes mellitus was present in 41.4% [95% CI (41.4–51.1)], hypertension in 39.8% [95% CI (35.1–44.6)], and coronary artery disease (CAD) in 15.2% [95% CI (11.8–18.8)]. At the time of presentation, shortness of breath was present in 73.6% [95% CI (69.1–77.7)], fever in 64.92% [95% CI (60.1–69.4)], and cough in 46.1%, [95% CI (41.1–50.8)]. Deranged laboratory parameters were lymphopenia in 90.2% [95% CI (86.8–92.7)], transaminitis in 59.7% [95% CI (54.8–64.3)], and hypercreatinemia in 37.7% [95% CI (33.1–42.5)]. Complications manifested were acute respiratory distress syndrome (ARDS) in 78.3% [95% CI (74–82.1)] and shock in 54.7% [95% CI (49.8–59.5)]. Median time duration between onset of symptom and hospital admission was 5 days (interquartile range (IQR) = 3–5 days) and median length of hospital stay was 9 days (IQR = 4–14 days). Conclusion During the first pandemic wave, COVID-19 related mortality was 2.37 times higher among males, 2.14 times in the age group >60 than 40%) were type II diabetes mellitus and hypertension. The most common associated symptoms (>60%) were shortness of breath and fever. Lymphopenia was seen in >90% cases while liver involvement in 60% and kidney in 38% cases. Median hospital stay was doubled the prehospital illness. How to cite this article Tendulkar P, Pandey P, Panda PK, Bhadoria AS, Kulshreshtha P. Descriptive Epidemiology of COVID-19 Deaths during the First Wave of Pandemic in India: A Single-center Experience. Indian J Crit Care Med 2022;26(1):71–75.