Increasing dependence on smartphones results in the appearance of psychological problems, especially among young people. This study aims to determine the rates of alexithymia and its relationship with smartphone addiction and psychological distress in university students. Methods: A total of 2616 students (mean age = 22.5±3.5 years; 73.1% female) from universities in Egypt, Oman, and Pakistan were included in a cross-sectional and comparative study conducted through a web survey during the COVID-19 pandemic from October to December 2021. The following scales were used: Toronto Alexithymia Scale (TAS-20), Depression Anxiety Stress Scale (DASS-21), and Smartphone Addiction Scale-Short Version (SAS-SV). The survey also included questions related to sociodemographic and smartphone usage patterns. Results: Students scoring above the TAS-20 cutoff point were significantly more likely to have smartphone addiction (χ2 (1) = 45.41; p 0.001) and psychological distress (χ2 (1) = 246.31; p 0.001). Likewise, smartphone addiction was significantly associated with psychological distress (χ2 (1) = 57.46; p 0.001). However, at each of the TAS20, SAS-SV, and DASS-21 variables, there were significant differences between the students of the three countries (p 0.050, p 0.010, and p 0.010, respectively); smartphone addiction was highest in Oman, while alexithymia and psychological distress were most severe in Egypt. Women scored higher than men on SAS and TAS scales (p 0.001). Students who used social media frequently were more prone to smartphone addiction. Conclusions: Understanding cultural and socioeconomic factors (such as living standards, technology accessibility, and social interaction patterns) is crucial for generating strategies to improve the psychological well-being of the youth of different regions and countries. Further, this study confirms the findings of recent studies indicating the heightened university students’ psychological vulnerability during the COVID-19 pandemic.