Research from around the world shows important differences in the impact of the COVID-19 pandemic and lockdowns on mental health. This study examined the extent of mental health challenges (depressive and anxiety symptoms and daily life difficulties) and their associations with pandemic- and response-related factors during the first lockdown in Lebanon, which happened amid a severe economic crisis and socio-political turmoil. Data come from a cross-sectional internet-based survey (May-June 2020). Association of depressive (Patient Health Questionnaire (PHQ-9)) and anxiety symptoms (Generalized Anxiety Disorder (GAD-7)) with outbreak-related worries and knowledge, information sources, and confidence and satisfaction in response measures were estimated using logistic regression adjusted for sociodemographic and socioeconomic indicators. Among 510 participants (mean age 36.1±11.3; 69.4% women), 32.3% had elevated depressive and 27.3% had elevated anxiety symptoms; younger age, unemployment, loss of employment, and lower income were related to more mental health symptoms. Most prevalent daily life challenges were feelings of uncertainty (74.5%) and financial (52.2%) and emotional (42.2%) difficulties; these and all other daily life difficulties (work-related, caregiving, and online learning) were significantly higher among participants with higher depressive and anxiety symptoms. Higher outbreak-related worries were associated with higher depressive (OR = 1.36, 95% CI = 1.20,1.53) and anxiety symptoms (OR = 1.47, 95% CI = 1.30,1.67). Higher pandemic-related knowledge, reliance on and trust in local health agencies and professionals' information, and satisfaction and confidence regarding governmental and health institutions' response were all related to lower mental health symptoms. Results show that mental health burden in Lebanon during the first lockdown (when the COVID-19 outbreak was still minimal) is among the highest reported worldwide and highlight elevated emotional and financial tolls and widespread impact on daily life. In this high-burden and multiple-challenges context, results suggest an important role for the healthcare body, knowledge, and trust in the institutions managing the response.