Background: Prior studies have indicated the complex relationships of smartphone use and smartphone addiction with mental health and life satisfaction. The purpose of this study was to investigate the structural relationships among smartphone use, smartphone addiction, mental health problems (e.g., depression, anxiety, stress [DAS] and satisfaction with life [SWL]). Methods: Cross-sectional data were collected by convenience sampling via an online survey of undergraduate students at a Midwestern university in the United States. The sample size of601 collected from undergraduate students that owned a smartphone and completed responses to the variables was utilized in this study. We assessed the hypothesized variables, including smartphone use, smartphone addiction, and mental health outcomes variables on a Likert-type scale. Structural analysis was used to examine the relationships. Results: Results suggested that smartphone use had a significant negative association with DAS symptoms (β = -.31, t = -3.81, P < .001) and was positively associated with SWL (β =.25, t = 3.41, P < .001). However, smartphone use had a significant positive relationship with smartphone addiction (β = .48, t = 5.51, P < .001). Smartphone addiction was positively related to DAS (β = .44, t = 6.33, P < .001), but it was not related to SWL (β = -.08, t = -1.26, P > .05). Conclusion: This study enhances our understanding of the associations between smartphone use and the health and well-being of undergraduate students. Implications for supporting their psychological health are discussed.