Background: The western region of Saudi Arabia is the most populous and diverse. This study aimed to identify the types and distribution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants causing cases of coronavirus disease 2019 (COVID-19) in this region in June 2021. Methods: We conducted a cross-sectional study. All genetically tested COVID-19 patients were included. We investigated the types, distribution, and magnitude of SARS-CoV-2 variants among cases of COVID-19 in June 2021. We gathered patient demographic data, clinical profiles, and epidemiology data. Results: Of 115 COVID-19 confirmed patients (mean age, 40 years), 56.5% were males and 43.5% were females. Of those vaccinated, 47.1% had received a one-dose vaccination; 52.9% had received two-dose vaccinations, and 23.6% were unvaccinated. Of those vaccinated, 72.1% had received the Pfizer BioNTech vaccine, and 16.5% had received the Oxford-AstraZeneca vaccine. The Delta variant of SARS-CoV-2 was prevalent in most (87.8%) patients. Among those infected, 28.8% reported contact with another COVID-19 case, and 19.8% reported a travel history. Most cases (68.6%) were moderate, 99.4% of patients recovered, and one patient died from COVID-19. Conclusion: Most of the cases were primary infections, and the Delta variant was predominant and highly transmissible. Most COVID-19 patients were mild to moderately ill. A better understanding of the transmission and diagnosis of these variants will help in early detection and reduction of infection by application of the best preventive measures. Categories: Infectious Disease, Public Health, Epidemiology/Public Health