Excessive, problematic smartphone use (PSU) has demonstrated relationships with depression and anxiety severity across studies. However, less is known about psychopathology-related variables that may mediate relations between depression/anxiety with PSU – especially variables involving emotional regulation processes. We recruited 261 college students for a repeated-measures web survey, administered self-report measures of depression, anxiety sensitivity, distress tolerance, mindfulness, smartphone use frequency, and PSU; one month later, participants completed these measures again. We tested a model where depression severity and anxiety sensitivity predicted distress tolerance and mindfulness, in turn predicting smartphone use frequency, and one-month PSU severity, adjusting for age and sex. Distress tolerance and mindfulness were inversely associated with levels of PSU. Distress tolerance mediated relations between anxiety sensitivity and levels of PSU. Mindfulness mediated relations between both depression and anxiety sensitivity with PSU severity. Results are discussed in the context of emotion regulation theory and compensatory internet use theory, with clinical implications for emotion regulation skills training and mindfulness in offsetting PSU.