Background: Given the high risk of COVID-19 mortality, patients with cancer are not only vulnerable to physical consequences of COVID-19 infection, but also to adverse psychological outcomes, including fear of COVID-19. Without intervention, psychological distress in patients with cancer can lead to worsening symptoms, poor quality of life, and lower survival. We sought to evaluate the association between fear of COVID-19 and psychological distress for under-resourced patients with cancer during the pandemic. Methods: This observational, longitudinal survey study, fielded during early (May 20- July 11, 2020) and later pandemic (December 2-December 23, 2020), evaluated the pandemic’s impact on patients with cancer receiving Patient Advocate Foundation (PAF) services from July 2019 – April 2020. Questions focused on individual experiences with COVID-19 and psychological, emotional, physical, and material effects from the pandemic. The validated Fear of COVID-19 Scale was used to determine fear of COVID-19. Psychological distress was determined using a four-item questionnaire by Holingue et al. (score range 4 – 16). Means and 95% confidence intervals (CI) were estimated using generalized estimating equation modeling with repeated measures to assess the effect of fear of COVID-19 on psychological distress early and later in the pandemic. Models adjusted for age, sex, race/ethnicity, region, annual household income, household size, marital status, employment status, Area Deprivation Index category, Rural-Urban Commuting Code category, cases per 100,000 in county of residence, cancer type, and number of comorbidities. Results: Amongst 1199 survey respondents, 94% considered themselves high risk for COVID-19. 448 respondents completed both the first and second survey. The majority of respondents were female (72%) and age 56-75 (55%); 40% were Black, Indigenous, or Persons of Color. In adjusted models of respondents who completed the early pandemic survey, respondents with more fear of COVID-19 had a higher mean psychological distress score (10.21; 95% CI 9.38-11.03) compared to respondents with less fear (7.55; 95% CI 6.75-8.36). Among those who completed the later pandemic survey, median fear of COVID-19 decreased (20 vs 19)median distress scores remained the same (8); respondents with more fear of COVID-19 had a higher mean psychological distress score (9.98; 95%CI 9.04-10.92) compared to respondents with less fear (7.87; 95%CI 6.98-8.76). Conclusions: Fear of COVID-19 was linked to psychological distress and persisted throughout the pandemic among under-resourced patients with cancer. Timely psychosocial support is critical to meet increased care needs experienced by patients with cancer during the COVID-19 pandemic. Given these results, fear of COVID-19 could be considered as a trigger to integrate psychological interventions in patients with cancer to treat psychological distress.