Background: The uncertainty and limited predictability surrounding the course of the coronavirus disease 2019 (COVID-19) pandemic has had negative consequences on people’s psychosocial health status. The study aimed to explore the impact of COVID-19 on the psychosocial status of Saudi and Egyptian population using a comparative design. A descriptive cross-sectional study was conducted between April 10 and 30, 2020, considering 517 participants from both countries (230 Egyptians, and 287 Saudis). For the research purpose, psychosocial status was defined as the general psychological and social conditions of the person that encompasses the anxiety, depression, and obsession feelings of the individual. Tools used were COVID-19 Anxiety Scale (CAS), Depressive symptoms questionnaire (DSQ), and obsessive-compulsive disorder questionnaire (OCD). Results: The mean psychosocial distress scores were significantly higher among Egyptian participants compared to Saudis. Anxiety was significantly lower among Saudis older than 55 years old compared to Saudis from younger ages. Among Egyptian participants, those who were married, employed, and/or older than 55 years had significantly lower depression and OCD scores; among Saudis, women and unemployed had significantly higher depression and OCD scores. Overall, anxiety, depression, and OCD scores had a significantly positive correlation with one another. Conclusions: Egyptians had greater prevalence rates of anxiety, depression, and OCD than Saudis. Many factors served as significant independent predictors for anxiety, depression, and OCD levels including gender, nationality, and employment status. The study reveals some factors associated with psychological impact that may be used to formulate psychological interventions to assist patients with vulnerable mental health statuses during COVID-19 pandemic and future health emergencies.