This study examined the relationship between COVID-19 stress, self-regulation, and smartphone addiction among university students. It also assessed whether self-regulation mediates the relationship between COVID-19 stress and smartphone addiction. The participants comprised 346 students enrolled in G city university. Data were analyzed using SPSS and AMOS to generate descriptive statistics, perform a correlation analysis, and create a structural equation model. The main findings were as follows. First, COVID-19 stress had a negative correlation with self-regulation, but a positive correlation with smartphone addiction. A negative correlation was observed between self-regulation ability and smartphone addiction. Secondly, self-regulation partially mediated the relationship between COVID-19 stress and smartphone addiction. The results will inform educational and counseling interventions aimed at preventing smartphone addiction among university students living in the era of the COVID-19 pandemic.