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The coronavirus disease 2019 (COVID-19) pandemic has created a public health crisis. This study aimed to evaluate the diagnostic performance of the Panbio and STANDARD Q COVID-19 antigen rapid diagnostic tests (RDTs) against the real-time polymerase chain reaction (RT-PCR) at one of the largest hospitals in southern Ethiopia. Nasopharyngeal samples, which were collected during the pandemic from individuals suspected of COVID-19 and stored at − 70 °C, were analyzed in June and July 2022. The performance of the Panbio COVID-19 antigen tests was evaluated in 200 randomly selected nasopharyngeal samples (100 positives and 100 negatives for severe acute respiratory syndrome 2 by RT-PCR). The STANDARD Q test was evaluated using 100 positive and 50 negative samples. The respective sensitivity, specificity, positive predictive value and negative predictive values were 88%, 99%, 98.9% and 89.2% for the Panbio test and 91%, 98%, 98.9% and 84.5%, for the STANDARD Q test. The kappa values were 0.87 for the Panbio and 0.86 for the STANDARD Q test. Based on the findings presented here, the RDTs could be utilized as an alternative to conventional RT-PCR when it is challenging to diagnose COVID-19 owing to a lack of time, skilled lab personnel, or suitable equipment or electricity. [ABSTRACT FROM AUTHOR]