Gremlin-1 is associated with lung disease and plays a role in the initiation and progression of pulmonary fibrosis. This suggests that Gremlin-1 may be associated with lung involvement in COVID-19 and poor clinical outcomes and warrants further investigation. This prospective, cross-sectional, single-blind study was the first to investigate Gremlin-1 levels in COVID-19 patients and whether Gremlin-1 levels could be used to predict and guide clinical follow-up in outpatients and inpatients. In this context, serum Gremlin-1 levels were measured and compared in 2 groups of patients who were diagnosed as positive for COVID-19 by RT-PCR and were followed up as outpatients (n = 28) or required hospitalization (n = 30). The median Gremlin-1 values were statistically significantly different between outpatients and intensive care unit patients (0.367 ng/mL [IQR = 0.377], 1.858 ng/mL [IQR = 2.245], respectively) (P < .0001). The area under the ROC curve value to determine the discriminative power of Gremlin-1 was found to be 0.772 (95% CI: 0.672-0.871; P < .0001), and the cutoff value of Gremlin-1 to discriminate between outpatients and hospitalized patients was found to be 1.242 ng/mL with 66.7% sensitivity and 67.2% specificity. Serum Gremlin-1 level is an important biomarker that can be used as a clinical decision-making tool for COVID-19 positive patients.