Objectives: To identify differences in the clinical and epidemiologic characteristics of patients during the first and second waves of the COVID-19 pandemic at the EsSalud Lambayeque health care network, Peru. Methods: An analytical cross-sectional study of 53,912 patients enrolled during the first and second waves of COVID-19 was conducted. Cluster analysis based on clustering large applications (CLARA) was applied to clinical-epidemiologic data presented at the time of care. The two pandemic waves were compared using clinical-epidemiologic data from epidemiologic surveillance. Results: Cluster analysis identified four COVID-19 groups with a characteristic pattern. Cluster 1 included the largest number of participants in both waves, and the participants were predominantly female. Cluster 2 included patients with gastrointestinal, respiratory, and systemic symptoms. Cluster 3 was the “severe” cluster, characterized by older adults and patients with dyspnea or comorbidities (cardiovascular, diabetes, obesity). Cluster 4 included asymptomatic, pregnant, and less severe patients. We found differences in all clinical-epidemiologic characteristics according to the cluster to which they belonged. Conclusion: Using cluster analysis, we identified characteristic patterns in each group. Respiratory, gastrointestinal, dyspnea, anosmia, and ageusia symptoms were higher in the second COVID-19 wave than the first COVID-19 wave.