Introduction Efficient and practical healthcare based on prognostic indicators can reduce morbidity and mortality in hospitalized COVID-19 patients. Soluble urokinase plasminogen activator receptor (suPAR) predicts clinical outcomes and respiratory failure in SARS-CoV-2 patients, but additional research is needed. Among other characteristics, we aimed to evaluate the predictive value of suPAR in COVID-19 patients. Methods This observational study was conducted at the All India Institute of Medical Sciences in New Delhi between January and April 2022. Patients within the age range from 18 to 85 years with mild, moderate, or severe COVID-19 infections were included in the study. Twenty-one patients (group 1) had positive RT-PCR throat and nasal swabs. Nine patients (group 2) with fever but without COVID-19 were recruited as controls. Ninety patient samples were tested for suPAR on days 1, 5, and 10 utilizing suPARnostic AUTO Flex ELISA kits (ViroGates, Denmark). Results The median age was 59 years in both groups. COVID-19 was mild in six patients (29%), moderate in seven patients (33%), and severe in eight patients (38%). At a median follow-up of 10 days, 8 out of 21 patients (38%) in group 1 died, while none in group 2 died. Patients' median suPAR levels were 4.35 ng/ml on day 1, 4.68 ng/ml on day 5, and 4.37 ng/ml on day 10. In the control group, suPAR levels were 1.6 ng/ml on day 1, 1.7 ng/ml on day 5, and 2.02 ng/ml on day 10. The suPAR levels were statistically significant on day 1 (p = 0.004), day 5 (p = 0.04), and day 10 (p = 0.007) between the patient and the control groups. Conclusion Patients who died had higher suPAR levels on days 1 (p = 0.007), 5 (p = 0.01), and 10 (p = 0.03) than survivors. The suPAR cut-off ≥ 3.64 (AUC = 0.82) predicts mortality with 88% sensitivity and 73% specificity.