Background: Medical students’ psychological response to societal lockdown during the covid-19 pandemic has not been studied much. Our aim was to assess levels of anxiety and depression among medical students during the initial stages of the pandemic in Nepal and relate their distress to psychosocial and other relevant situational variables.Materials and Methods: A cross-sectional study with an online questionnaire was conducted among medical students at different colleges in Nepal. Hospital Anxiety and Depression Scale (HADS) detected manifestations of anxiety and depression. The covariates were explored by logistic regression analyses.Results: A total 416 medical students [mean age: 22.2 (2.1); males 57.7%, females 42.3%] participated. HADS-anxiety scores [mean: 7.1(4.3)] were significantly and positively correlated with HADS-depression [mean: 5.9 (4.1)] (r=0.695; p<0.001). Point prevalence of total HADS caseness (HADS-T) was 26.7%. Specific HADS-defined caseness were: anxiety (HADS-A) 11.8%, depression (HADS-D) 5.5%, and comorbid anxiety and depression (HADS-cAD) 9.4%. All four types of caseness were significantly more prevalent among students with a history of mental problems (AOR=4.7, 3.2, 2.6, and 3.2 respectively). HADS-T was higher among those with a concurrent physical illness (AOR=2.4). HADS-T, HADS-A and HADS-D scores were higher among the age group >22 years (AOR= 2.2, 2.5 and 4.4 respectively). HADS-cAD was almost three-times higher among those with a possible COVID-19 exposure (AOR=2.8).Conclusion: A significant number of medical students in Nepal suffered from high levels of anxiety and depression during the covid-19 shut-down. The students in the higher (>22 years) age group, those with past mental disorders, a possible covid-19 exposure, and a concurrent physical illness showed elevated levels of anxiety and/or depression.