The purpose of the present study was to identify the protective and risk factors related to psychological distress during COVID-19 in an Israeli sample. An online survey was administered from April 19 to May 2, 2020, while a strict lockdown was in place. Participants were recruited by snowball sampling. Psychological distress was evaluated using the Generalized Anxiety Disorder questionnaire (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9). Risk and protective factors for psychological distress were assessed on the Multi-dimensional Perceived Social Support (MSPSS), the coping strategies (COPE), the Life Orientation Test (LOT), and the Gratitude questionnaire. Out of the 655 valid questionnaires collected (from participants ranging in age from 18 to 86, 246 males, 409 females), 138 (21.3%) were positive for moderate to very severe depression and 87 (13.2%) for moderate to extremely severe anxiety. Participants who were screened for depression and anxiety were more likely to be women and young adults (18–24). After adjusting statistically for gender, age, and socioeconomic status, depression and anxiety remained significantly associated with both emotion-focused (PHQ-β =.437, p < .001, GAD-β=.441, p < .001) and problem-focused (PHQ-β =−.219, p < .001, GAD-β=−.143, p < .001) coping strategies, as well as on the social support (PHQ-β =−.167, p < .001, GAD-β=−.155, p < .001), life orientation (GAD-β=−.09, p < .001), and gratitude scales (PHQ-β =−.07, p < .001). Levels of anxiety and depression were generally associated with gender (women), age (younger population), socioeconomic status (low), and an emotion-focused strategy as risk factors. A problem-focused strategy, social support, life orientation, and gratitude served as protective factors above and beyond personal background.