The worldwide spread of the coronavirus disease (COVID-19), the absence of medical treatment and vaccination, the delayed onset of symptoms, and the rapid human-to-human transmission have led the vast majority of countries to impose strict social distancing procedures. Whereas it appears that social distancing is an effective strategy for mitigating spread, it may also result in a variety of unintended negative consequences to individuals’ psychological well-being and mental health. During the peak of the COVID-19 pandemic, the present study examined associations among some demographic variables (gender, age, marital and working statuses, and having a family member or a friend infected with COVID-19), acceptance of social distancing, mood changes, and quality of life (QoL) in Qatar, a high-income Middle Eastern Arabic-speaking country. Older, married, and working participants were more accepting of social distancing than younger, unmarried, and non-working participants, respectively. Participants indicated that, during this time, they became more distressed, upset, scared, irritable, nervous, and afraid, and less inspired and determined. In a stark contrast, more individuals indicated that they became more interested, alert, and attentive, whereas higher percentages of participants reported feeling less guilty, hostile, and ashamed. Social distancing correlated positively with negative affect, whereas social avoidances correlated positively with positive affect and with physical, psychological, social, and environmental QoL. Finally, positive affect correlated positively, and negative affect correlated negatively, with these four domains of QoL. These results highlight the need for public health and clinical providers to consider peoples’ psychological well-being and mental health during the COVID-19 pandemic.