Poor sleep and alterations in the stress-sensitive hypothalamic–pituitary–adrenal (HPA) axis may be mechanisms through which loneliness impacts adolescents’ well-being. Few researchers have explored whether daily variation in experiences of social connection predict day-to-day variation in sleep and HPA axis activity among adolescents navigating the college context. Using daily diary reports of social connection, objective measures of sleep (actigraphy), and naturalistic salivary assessment, the present study examined within-person associations between first-year college students’ social connection during the day and sleep that night, as well as diurnal cortisol activity the following day. The present study also explored trait-level loneliness as a moderator of these associations after adjusting for baseline loneliness assessed in high school. Seventy-one first-year college students (23 % male; M age = 18.85; 52 % non-Hispanic White) completed daily diary reports, wore a wrist-based accelerometer (actigraph watch), and provided saliva samples five times daily across three consecutive weekdays. The results from hierarchical linear models indicated that within-person increases in daily social connection were significantly associated with longer time spent in bed and more actual time asleep that night only for adolescents high on loneliness. Within-person increases in daily social connection were associated with a greater cortisol awakening response (CAR) the next day, regardless of trait loneliness. These findings illustrate that more daily social connection with others than usual may predict improved sleep quantity for lonely adolescents and a physiological index of anticipating upcoming daily demands (CAR) in general. Future intervention programs might consider including strategies focused on enhancing daily social interactions among adolescents starting college, particularly for lonely adolescents.