Objective: Loneliness is a well-established risk factor for poor physical health. Much less is known about how loneliness affects patient-reported outcomes (PROs), such as somatic symptoms, which are increasingly important for guiding symptom management and assessing quality of patient care. The current study investigates whether (a) loneliness and social isolation predict cold symptoms independent of each other, and (b) whether loneliness is a more robust risk factor than objective social isolation for experiencing cold symptoms. Method: As part of a larger parent study, 213 healthy participants completed the Short Loneliness Scale (LON) and the Social Network Index (SNI) at baseline. They were given nasal drops containing rhinovirus 39 (RV39; i.e., a common cold virus), then quarantined for 5 days during which they reported on subjective cold symptoms in addition to being monitored for objective indicators of infection. Data from 160 of the participants (who were infected with the virus) were used in the present analyses. Results: A hierarchical multiple regression revealed that baseline loneliness predicted self-reported cold symptoms over time (assessed via area under the curve), over and above demographic variables, season of participation, and depressive affect. Interestingly, social network size and diversity did not predict cold symptoms. Conclusions: These findings suggest that the perception of loneliness is more closely linked to self-reported illness symptoms than objectively measured social isolation. Assessing psychosocial factors such as loneliness when treating and evaluating the common cold could contribute to health care practitioners’ understanding of their patients’ experiences with acute illness.