Introduction: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to persist due to mutations resulting in newer, more infectious variants of concern. The initial government response to COVID-19 failed to engage the private sector. Engaging the private sector could have bolstered the national capacity to process diagnostic tests and track variants of concern for disease for public health surveillance. We aimed to leverage an ongoing private SARS-CoV-2 testing laboratory’s infrastructure to monitor SARS-CoV-2 variants in two large California counties.Methods: Study enrollment was offered to adults aged 18 years or older in Los Angeles County and Riverside County in California who recently tested positive for SARS-CoV-2 by polymerase chain reaction (PCR) with a cycle threshold value less than or equal to 30 cycles. Trained healthcare workers directly observed self-collection of oral fluid or anterior nares specimens within 5 days of study enrollment. Specimens were transported and stored at 8°C or cooler. RNA was extracted from samples. Samples underwent library preparation and were sequenced. Sequencing data were filtered by quality criteria. High-quality genomic data were analyzed to identify SARS-CoV-2 lineages. Participant and genomic data were analyzed using statistical tools and visualized with toolkits. The study was approved by Advarra Institutional Review Board (Pro00053729).Results: From May 27, 2021 to September 9, 2021, 503 participants were enrolled and underwent specimen collection. Of those enrolled, there were 238 (47.3%) females, 329 (63.6%) vaccinated, and 221 (43.9%) of Hispanic or Spanish origin. Of the cohort, 496 (98.6%) had symptoms at the time of collection. Among the 503 participants, 443 (88.1%) nasal specimens and 353 (70.2%) oral specimens yielded sequencing results. Over our study period, the prevalence of the Alpha variant of SARS-CoV-2 decreased (initially 23.1% [95% confidence interval (95% CI): 0% to 0.49%] to 0% [95% CI: 0.0% to 0.0%]) as the prevalence of the Delta variant of SARS-CoV-2 increased (initially 33.3% [95% CI: 0.0% to 100.0%] to 100.0% [95% CI: 100.0% to 100.0%]). A strain that carried mutations of both Delta and Mu was identified.Conclusion: We found that outpatient SARS-CoV-2 variant surveillance could be conducted in private laboratory in a timely and accurate manner. The prevalence of different variants changed over time. A higher proportion of nasal specimens yielded results when compared to oral specimens. Timely outpatient SARS-CoV-2 variant surveillance could be used for public health efforts to identify changes in SARS-CoV-2 strain epidemiology in local areas. Government agencies should engage private laboratories in the surveillance of diseases that threaten the public’s health to supplement national disease reporting networks.