BACKGROUND: Food insecurity has increased during the COVID-19 pandemic, affecting an estimated 260 million people. However, little evidence is available on how pandemic-related characteristics influence food security in a high-altitude population. The objective of this study was to assess factors associated with food insecurity in high-altitude Peruvian cities during the second epidemic wave of COVID-19. METHODS: A retrospective, cross-sectional study was conducted in eight Peruvian cities over 1,500 m above sea level. An online survey measuring food security, presence of anxiety & depressive symptoms, sleep quality, post-traumatic stress disorder (PTSD), resilience, and sociodemographic characteristics was disseminated through social networks between December 2020 and February 2021. Generalized linear models were used to identify an association between the study variables. RESULTS: Of 700 participants, the median age was 23 years, and more than half were female (56.7%). The prevalence of food insecurity was 37.1%. Anxiety symptoms, depressive symptoms, and PTSD were present in 72.7%, 64.1%, and 15% of respondents, respectively. The prevalence of food insecurity was higher in people with fair (PR: 1.60, 95% CI: 1.23-2.07) and very bad perception of their health (PR: 4.06, 95% CI: 2.63-6.26), individuals seeking mental health support (PR: 1.42, 95% CI: 1.25-1.62), and in those who lost their job due to the pandemic (PR: 1.82, 95% CI: 1.62-2.04). Having moderate (PR: 1.52, 95% CI: 1.26-1.83) and moderate to severe depressive symptoms (PR: 1.58, 95% CI: 1.11-2.27) also increased the prevalence of food insecurity. CONCLUSION: During the pandemic, the prevalence of food insecurity has increased in the Peruvian high-altitude population, revealing the need for preventive strategies. Identification of pandemic-related characteristics that influence food insecurity can guide interventions in at-risk individuals and reduce the long-term impact of this problem on overall health and quality of life.