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This study examines differences in adjustment, perceived stress, coping strategies, and COVID-19 adjustment between STEM and non-STEM university students during the early COVID-19 pandemic in the United States. Results indicated significant differences in academic adjustment and coping strategies, with non-STEM students showing better academic adjustment and higher reliance on avoidance strategies. No significant differences were found in overall stress levels. Multivariate regression analyses identified significant predictors of perceived stress, emphasizing the importance of academic and personal-emotional adjustment. Findings suggest tailored interventions for improving student well-being, particularly for STEM students facing academic adjustment challenges. Insights from this study can inform strategies for supporting university students during crisis periods, enhancing their overall well-being and academic success.