Facebook use is very popular among young people, but many open issues remain regarding the individual traits that are antecedents of different behaviours enacted online. This study aimed to investigate whether the relationship between self-esteem and the amount of time on Facebook could be mediated by a tendency towards social comparison. Moreover, three different modalities of Facebook use were distinguished, i.e., social interaction, simulation, and search for relations. Because of gender differences in technology use and social comparison, the mediation models were tested separately for males and females. Data were collected by means of a self-report questionnaire with a sample of 250 undergraduate and graduate Italian students (mean age: 22.18 years). The relations were examined empirically by means of four structural equation models. The results revealed the role of orientation to social comparison in mediating the relations between low self-esteem and some indicators of Facebook use, i.e., daily hours on Facebook and the use of Facebook for simulation. For females, the use of Facebook for social interaction was directly influenced by high self-esteem and indirectly influenced by low self-esteem. Globally, the dimension of social comparison on Facebook emerged as more important for females than for males.