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(1) Background: Laboratory-based molecular assays are the gold standard to detect SARS-CoV-2. In resource-limited settings, the implementation of these assays has been hampered by operational challenges and long turnaround times. Rapid antigen detection tests are an attractive alternative. Our aim is to evaluate the clinical performance of two SARS-CoV-2 rapid antigen tests during a high transmission period. (2) Methods: A total of 1277 patients seeking SARS-CoV-2 diagnosis were enrolled at four health facilities. Nasopharyngeal swabs for rapid antigen and real time PCR testing were collected for each patient. Sensitivity, specificity, positive and negative predictive values, misclassification rate, and agreement were determined. (3) Results: The overall sensitivity of Panbio COVID-19 was 41.3% (95% CI: 34.6–48.4%) and the specificity was 98.2% (95% CI: 96.2–99.3%). The Standard Q had an overall sensitivity and specificity of 45.0% (95% CI: 39.9–50.2%) and 97.6% (95% CI: 95.3–99.0%), respectively. The positive predictive value of a positive test was 93.3% and 95.4% for the Panbio and Standard Q Ag-RDTs, respectively. A higher sensitivity of 43.2% and 49.4% was observed in symptomatic cases for the Panbio and Standard Q Ag-RDTs, respectively. (4) Conclusions: Despite the overall low sensitivity, the two evaluated rapid tests are useful to improve the diagnosis of symptomatic SARS-CoV-2 infections during high transmission periods. [ABSTRACT FROM AUTHOR]