Background: There is evidence that anxiety and stress increased among college students during the COVID-19 pandemic.However, less is known about daily experiences of affect, worry, substance use behaviors, experiences of pleasure, concern overfood security, experiences of bias or discrimination, feelings of belongingness, and other indicators of well-being and how theyvary across days in this population.Objective: This study surveyed a wide range of indicators of health and well-being in daily life over 21 days with a sample ofcollege students in a large university system in the United States during the pandemic. The overall variance in each daily measurewas partitioned to reflect the proportion due to (1) between-person differences versus (2) within-person, day-to-day variability.This is important because measures that vary primarily due to between-person differences may be more amenable to interventionsthat target particular students, whereas measures that vary more due to day-to-day variability may be more amenable to interventionsthat target day-level contextual factors.Methods: A sample of 2068 young adult college students (aged 18-24, mean 19.8, SD 1.3 years; 66.6% women) completed abaseline survey; 97.3% (n=2012) then completed up to 21 consecutive daily surveys that assessed a comprehensive set of dailymarkers of health, behavior, and well-being. The daily diary study produced a total of 33,722 person-days.Results: Among all person-days, a minority were substance use days (eg, 14.5% of days involved alcohol use, 5.6% vaping,and 5.5% cannabis). Experiences of pleasure were reported on most (73.5%) days. Between-person differences explained morethan 50% of the variance in numerous indicators of health and well-being, including daily vaping, cannabis use, other illicitsubstance use, experiences of bias or discrimination, positive affect, negative affect, worry, food insecurity, and feelings ofbelonging at the university. In contrast, within-person differences explained more than 50% of the variance in daily alcohol use,cigarette use, stress, experiences of pleasure, where the student slept last night, and physical activity.Conclusions: College student health and well-being are multifaceted, with some aspects likely driven by person-levelcharacteristics and experiences and other aspects by more dynamic, contextual risk factors that occur in daily life. These findingsimplicate services and interventions that should target individual students versus those that should target days on which studentsare at high risk for poor experiences or behaviors