Background: To explore how sexual activity was impacted by coronavirus disease 2019 (COVID-19) lockdown measures in the general adult population. Methods: A cross-sectional survey was conducted among 6,003 Italian adults aged 18–74 years who were representative of the Italian general population. Study subjects were recruited at the time of the nationwide stay-at-home order (from April 27 to May 3, 2020). We identified characteristics associated with decreased frequency of sex during lockdown, differentiating between cohabiting and non-cohabiting subjects. Results: Over one-third (35.3%) of Italians reported to have changed their sexual activity during lockdown (8.4% increased and 26.9% decreased). When focusing on cohabitants (N = 3,949, 65.8%), decreased sexual activity (20.7%) was more frequently reported by men (22.3%; compared to women, multivariable odds ratio 1.23; 95% confidence interval, 1.05–1.44), younger subjects (P for trend