Purpose The COVID-19 pandemic has undoubtedly altered the routine of life and caused unanticipated changes resulting in severe psychological responses and mental health crisis. The study aimed to identify psycho-social factors that predicted distress among Indian population during the spread of novel Coronavirus. Method An online survey was conducted to assess the predictors of distress. A global logistic regression model was built, by identifying significant factors from individual logistic regression models built on various groups of independent variables. The prediction capability of the model was compared with the random forest classifier. Results The respondents (N = 1060) who are more likely to be distressed, are in the age group of 21-35 years, are females (OR = 1.425), those working on site (OR = 1.592), have pre-existing medical conditions (OR = 1.682), do not have health insurance policy covering COVID-19 (OR = 1.884), have perceived seriousness of COVID-19 (OR = 1.239), have lack of trust in government (OR = 1.246) and whose basic needs’ fulfillment are unsatisfactory (OR = 1.592). The ones who are less likely to be distressed, have higher social support and psychological capital. Random forest classifier correctly classified 2.3% and 17.1% of people under lower and higher distress respectively, with respect to logistic regression. Conclusions This study confirms the prevalence of high distress experienced by Indians at the time of COVID-19 and provides pragmatic implications for psychological health at macro and micro levels during an epidemiological crisis.