Background: Coronavirus has affected more than 100 million people. Most of these patients are hospitalized in isolation wards or self-quarantined at home. A significant percentage of COVID-19 patients may experience psychiatric symptoms. This study attempts to assess depressive, anxiety, and post-traumatic stress symptoms in home-isolated and hospitalized COVID-19 patients, besides whether the isolation setting affected these symptoms’ presentation. Results: The study involved 89 patients with confirmed COVID-19 virus, and the patients were divided into 2 groups: 43 patients in the home-isolated group (group A) and 46 patients in the hospital-isolated group (group B). The majority of subjects were male and married; also, they were highly educated. 30.2% from group A and 47.8% from group B had a medical occupation. There was a statistically significant difference (p= 0.03) between both groups in the presence of chronic disease. There was a statistically significant increase in suicidal thoughts in the home-isolated group (37.2%) (p = 0.008**). We found a statistically significant increase in the abnormal scores of Hospital Anxiety Depression Scale–Depression (HADS–Depression) in the home-isolated group (69.7%) compared to the hospital-isolated group (32.6%) (p <0.001**) which denotes considerable symptoms of depression. Moreover, we found that (32.6%) from the home-isolated group and (39.1%) from the hospital-isolated group had abnormal scores of Hospital Anxiety Depression Scale–Anxiety (HADS–Anxiety) which denotes considerable symptoms of anxiety. Also, we found 66.7% and 87.2% scored positive by the Davidson Trauma Scale (DTS) in the home-isolated group and hospital-isolated group, respectively. Which was statistically significant (p = 0.02**). On doing a binary logistic regression analysis of HADS and DTS with significantly related independent factors, we revealed that lower education levels and family history of psychiatric disorder were risk factors for abnormal HADS–Anxiety scores in COVID-19 patients. The medical occupation was a protective factor against having abnormal HADS–Depression scores in COVID-19 patients, while home isolation was a risk factor. On the contrary, the medical occupation was a risk factor for scoring positive in DTS in COVID-19 patients. Simultaneously, low levels of education and home isolation were protective factors. Conclusion: A significant number of patients diagnosed with the COVID-19 virus develop depressive, anxiety, and post-traumatic stress symptoms, whether they