OBJECTIVES: To investigate the prevalence of anxiety and depression among undergraduate nursing students during the COVID-19 pandemic and identify associated factors. METHODS: This study employed a concurrent mixed methodology, comprising a quantitative analytical cross-sectional web-based survey and a qualitative descriptive exploratory study using focus group discussions. The study was conducted at two university-based schools of nursing, one public and one private, in Karachi, Pakistan, from May to September 2021, during the third wave of the COVID-19 pandemic. Two questionnaires were employed: The Aga Khan University Anxiety and Depression Scale and COVID-19 related stressors. RESULTS: Among the study participants (n=300) 74%, were female. The 76.3% individuals' age between 20 to 29 years and 97.3% were single. The study reported 51% prevalence of anxiety and depression in COVID-19 were associated with females (OR=2.56, 95% CI:1.34-4.88), hostel residents (OR=1.9, 95% CI:1.02-3.52), final year students (OR=1.36, 95% CI:1.0021.870), e-learning (OR=1.74, 95%CI: 1.28-2.37), and those who had COVID-19 academic apprehensions and transition as future nurses (OR=1.13, 95% CI: 1.01.29). The qualitative analysis highlighted the theme, the realities of students' academic life amid COVID-19. This theme was emerged from three categories, l ack of preparedness, range of emotions and humble submissions. CONCLUSION: This study revealed a high prevalence (51%) of anxiety and depression among nursing students during the COVID-19 pandemic, particularly among females, hostel residents, and final-year students. Qualitative analysis highlighted challenges in academic adaptation amid COVID-19, revealing themes of lack of preparedness, a range of emotions, and humble submissions, stressing the need for targeted interventions and support systems.