Objective: To investigate the sex and gender differences in the impact of the isolation period implemented in response to the COVID-19 pandemic on individuals' sleep quality, empathy, and mood. Design: Data were collected between March 23 and June 7, 2020 on a sample of volunteers in the Canadian population. Six hundred and thirty-eight volunteers completed an online survey (∼30 min). Main Outcome and Measures: We first examined biological sex, gender, and sexual identity differences (both components of the ampler concept of gender) in sleep, empathy, and mood disturbances. Then, we assessed changes in sleep and mood over the course of the isolation period and tested for significant relationships between sleep variables, mood, and empathy. Results: We analyzed complete data for 573 participants (112 males and 459 females, 2 undisclosed, mean ± SD age = 25.9 ± 10.5 years, mean ± SD education = 16.2 ± 2.9 years). As compared to males, female participants reported lower quality of sleep, lower sleep efficiency, and greater symptoms of insomnia, anxiety, depression, and trauma. In addition, females reported higher scores than males on the IRI empathy scale and all its subcomponents. Similar results were found when stratifying by gender. Sleep and mood disturbances increased over the course of the isolation period in the whole sample. The most significant predictors of poor quality of sleep and insomnia were depression, anxiety, and trauma scores, especially in females; higher empathy trait was associated with higher depression, anxiety, and trauma scores, perhaps indicating a more positive role of fear and anxiety responses to the pandemic crisis. Significance and Conclusions: Sex and gender differences seem to play a role in the individuals' psychological and behavioral reactions to the COVID-19 pandemic. These differences need to be considered in planning targeted psychological interventions.