Background Multiple studies worldwide reported the clinical and epidemiological features of coronavirus disease 2019 (COVID-19) with limited reports form the Middle East area. Methods This is an observational study to describe the clinical and epidemiological features of 341 COVID-19 cases in the Eastern Province of Saudi Arabia over the first three months from reporting the first case in the country and identify factors associated with severity of the illness. Results The median age was 45 years and males were twice as affected as females (p value < 0.0001). The duration of viral shedding ranged from 9 to 36 days. The most common clinical presentations include fever, shortness of breath, cough, myalgia, sore throat, vomiting, and headache. Severe and critical cases were significantly higher in males compared to females (23% vs 8.7%), senior adults (> 65 years), Bengali ethnicity, and in patient with com-morbidities including diabetes, hypertension, and dyslipidemia (p-value = 0.001). Furthermore, case fatality rate was found to be 10% and was significantly higher in male gender compared to female (13.8%vs 2.6%), and in Asian ethnicity (17.9%) compared to Arabs (6%) and African counterparts (0) (p-value = 0.002). No association was found between viral load represented by the RT-PCR cycle threshold (Ct) values and severity of illness. Conclusion Age, gender and ethnicity are important predictors of COVID-19 severity while Cycle threshold (Ct) of SARS-CoV-2 RT-PCR test cannot be used as a predictor of criticality of illness.