Burnout is common among nurses and undermines their health, well-being and job performance. The purpose of this two-wave longitudinal study was to analyze the relationships between loneliness and three dimensions of burnout (i.e. exhaustion, cynicism and professional efficacy) in this professional group and to test whether these relationships are mediated by insomnia. A total of 520 nurses were assessed at two time points, T1 and T2, six months apart, with a set of self-reported questionnaires including the De Jong Gierveld Loneliness Scale (DJGLS), the Athens Insomnia Scale (AIS) and the Maslach Burnout Inventory - General Survey (MBI-GS). Socio-demographic and work-related characteristics were also recorded. Structural Equation Modeling (SEM) was used to analyze the data. The findings indicate that loneliness was positively associated with cynicism and negatively with professional efficacy, with both direct and total effects being statistically significant. However, the direct effect of loneliness on exhaustion was not confirmed, while the total effect was significant. Insomnia emerged as a significant mediator in each of these relationships. The present study clearly demonstrates the significance of the subjective appraisal of social connections and sleep problems in the development of burnout syndrome among nurses.