Background: Hospitalized patients may unknowingly carry severe acute respiratory coronavirus virus 2 (SARS-CoV-2), even if they are admitted for other reasons. Because SARS-CoV-2 may remain positive by reverse-transcriptase polymerase chain reaction (RT-PCR) for months after infection, patients with a positive result may not necessarily be infectious. We aimed to determine the frequency of SARS-CoV-2 infections in patients admitted for reasons unrelated to coronavirus disease 2019 (COVID-19). Methods: The University of Iowa Hospitals and Clinics is an 811-bed tertiary-care center. We use a nasopharyngeal SARS-CoV-2 RT-PCR to screen admitted patients without signs or symptoms compatible with COVID-19. Patients with positive tests undergo a repeat test to assess cycle threshold (Ct) value kinetics. We reviewed records for patients with positive RT-PCR screening admitted during July–October 2020. We used a combination of history, serologies, and RT-PCR Ct values to assess and qualify likelihood of infectiousness: (1) likely infectious, if Ct values were <29, or (2) likely not infectious, if 1 or both samples had Cts <30 with or without a positive SARS-CoV-2 antinucleocapsid IgG/IgM test or history of a positive result in the past 90 days. Contact tracing was only conducted for patients likely to be infectious. We describe the isolation duration and contact tracing data. Results: In total, 6,447 patients were tested on hospital admission for any reason (persons under investigation or admitted for reasons other than COVID-19). Of these, 240 (4%) had positive results, but 65 (27%) of these were admitted for reasons other than COVID-19. In total, 55 patients had Ct values available and were included in this analysis. The median age was 56 years (range, 0–91), 28 (51%) were male, and 12 (5%) were children. The most frequent admission syndromes were neurological (36%), gastrointestinal (16%), and trauma (16%). Our assessment revealed 23 likely infections (42%; 14 definite, 9 possible) and 32 cases likely not infectious (58%). The mean Ct for patients who were likely infectious was 22; it was 34 for patients who were likely not infectious. Mean duration of in-hospital isolation was 6 days for those who were likely infectious and 2 days for those who were likely not infectious. We detected 8 individuals (1 healthcare worker and 7 patients) who were exposed to a likely infectious patient. Conclusions: SARS-CoV-2 infection in patients hospitalized for other reasons was infrequent. An assessment of the likelihood of infectiousness including history, RT-PCR Cts, and serology may help prioritize patients in need of isolation and contact investigations.