The COVID-19 pandemic caused uncertainty and changing public health recommendations across the world as our understanding of the SARS-CoV-2 virus changed. Following a preliminary assessment by the World Health Organization, non-steroidal anti-inflammatory drugs were said to worsen symptoms and should be avoided before the recommendation was subsequently revoked. There also was pain associated with infection, leading to the hypothesis that use of over-the-counter pain medication increases may correlate with increases of SARS-CoV-2 infections. Wastewater samples were collected from two communities in Tempe, AZ from December 2019 to July 2020 (n = 35) and were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify levels of acetaminophen, ibuprofen and their metabolites, acetaminophen sulfate and carboxy-ibuprofen. Results showed 100% detection frequency of all analytes in all samples across the duration of the study. Mass loadings of acetaminophen (918.4 g day-1 +/- 354.8 g day-1) were higher than ibuprofen (182.9 g day-1 +/- 49.8 g day-1), potentially driven by flushing behaviors rather than consumption activities. However, ibuprofen was more heavily consumed than acetaminophen across all days of the study period. Comparisons to COVID-19 clinical cases data showed increased use in ibuprofen with increases in clinical cases loads, while acetaminophen showed no change, suggesting ibuprofen was the over the counter (OTC) medication of choice during the first wave of the pandemic.