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Abstract Background The Canadian government’s response to the ongoing COVID-19 pandemic included the implementation of several restrictive measures since March 2020. These actions sought to decrease social contact and increase physical distancing, including that within universities. Such constraints were required to impede the transmission of the virus; however, concerns remain about their impact on the sexual and intimate relationships of university employees and students. Aim This study examined the associations between COVID-19–related stress and sexual frequency, sexual satisfaction, and relationship satisfaction, also testing the mediating role of psychological distress. Methods The models were tested with Canadian data collected from university employees and students in 2 phases: the first wave in April-May 2020 (T1; n = 2754) and the second wave in November-December 2021 (T2; n = 1430), 18 months afterward. Participants completed self-report questionnaires online. Path analyses were performed to test the associations of the mediation models. Outcomes The principal outcomes included psychological distress determined via the Patient Health Questionnaire–4, relationship satisfaction measured via the Dyadic Adjustment Scale, and sexual satisfaction and sexual frequency ascertained through a single item each. Results Overall, COVID-19–related stress was associated with higher psychological distress, which in turn was related to lower sexual frequency, sexual satisfaction, and relationship satisfaction. Similar results were obtained with T1 and T2 data, indicating the mediating effect of psychological distress. Clinical Implications These findings increase scholarly comprehension of the negative associations between stress/distress and sexual and romantic relationships. Sexuality and close relationships are vital to the quality of human life; thus, targeted interventions should be developed to reduce COVID-19–related stress and its impact on sexual and romantic relationships to mitigate the long-term influences of this unique global challenge. Strengths and Limitations To our knowledge, this study is the first to use a large sample size and replicate findings in 2 waves. Nonetheless, it is limited by the use of cross-sectional data. Longitudinal studies with the same participants are mandated to better understand the evolution of these outcomes. Conclusion COVID-19–related stress and psychological distress were found among participating university students and employees and were associated with lower sexual satisfaction, sexual frequency, and intimate relationship satisfaction. These results were observed at the early onset of the pandemic and 18 months afterward, suggesting that the stress generated by the pandemic were not mere reactions to the onset of the pandemic but persisted over time.