HIV and other sexually transmitted infections (STIs) are on the rise nationally and internationally. The coronavirus 2019 (COVID-19) pandemic drove a shift toward telemedicine and prioritization of symptomatic treatment over asymptomatic screening. The impact in safety-net settings, which faced disproportionate baseline STI/HIV rates rooted in structural inequities, and where many patients lack telemedicine resources, is not yet known. This study describes the impact of COVID-19 on STI/HIV testing at an urban safety-net hospital. We used descriptive statistics to compare hospital-wide chlamydia, gonorrhea, syphilis, and HIV testing volume and positivity rates in the following periods: prepandemic (July 1, 2019-February 29, 2020), peak-pandemic (March 1, 2020-May 31, 2020), and postpeak (June 1, 2020-August 31, 2021). STI and HIV test volume dropped sharply in March 2020. STI testing during the peak-pandemic period was 42% of prepandemic baseline (mean 1145 vs. 2738 tests/month) and nadired in April 2020 (766 tests/month). Similarly, peak-pandemic HIV testing was 43% of prepandemic baseline (mean 711 vs. 1635 tests/month) and nadired in April 2020 with 438 tests/month, concentrated in emergency department and inpatient settings. STI and HIV testing rates did not return to baseline for a full year. STI and HIV test positivity rates were higher in the peak-pandemic period compared with the prepandemic baseline. Given the precipitous decline in STI and HIV testing during the pandemic, safety-net settings should develop low-barrier alternatives to traditional office-based testing to mitigate testing gaps, high positivity rates, and associated morbidity.