In the present study, we empirically examined the “fear of missing out” (FOMO) construct and its association with psychopathology-related and technology use measures. We carried out an internet-based survey with 296 undergraduate participants and administered self-report questionnaires of FOMO, frequency and type of smartphone use, problematic smartphone use (PSU), and scales of negative affectivity including depression, anxiety, stress, proneness to boredom, and rumination. The results demonstrated that FOMO was related to demographic characteristics (age, sex, race, and relationship status) but with small effect sizes. FOMO was related to all measures of negative affectivity, social use of a smartphone, as well as the severity of PSU. Tests of mediation indicated that each negative affectivity construct mediated the relationship between FOMO and PSU severity, and only rumination mediated relations between FOMO and smartphone use frequency. When reversing the predictor and mediating variables, FOMO mediated relations between negative affectivity and PSU severity. Finally, results demonstrated some support for a single-factor latent construct for FOMO, but male and female participants had a different pattern of factor loadings. Negative affectivity may be a key mechanism by which FOMO may drive PSU, but future research should clarify the directionality among these variables. Gender-related social connectedness differences characterize FOMO.