The global outbreak of the Coronavirus pandemic has created significant educational disparities worldwide. This study aims to investigate the effect of school closure and social distancing during the COVID-19 pandemic on the psychological well-being of gifted students in Nigeria. Three research questions guided this study with focus on understanding the relationship between school closure, social isolation, and the psychological well-being of these students. To conduct this investigation, a descriptive survey research design was adopted for the study. A total sample of seventy students were selected among gifted students from Junior Secondary Schools (JSS III) in Ila/Boluwaduro/Ifedayo administrative zone consisting of four local government areas in Osun State, southwest region of Nigeria using a multi stage random sampling technique. Firstly, an instrument titled: Mathematics Achievement Test (MAT) was constructed by the researchers for the selection of gifted students from intact classes in the sampled schools. Data collection involved the use of Ryff’s Psychological Well-being Scale (PWBS) and the Social Isolation and School Closure Perception Scale (SISCPS), developed by the researchers. The instruments used enjoyed 95.7% as only 67 were retrieved. Data analysis was done with SPSS, Mean, Standard Deviation, pearson product moment correlation and multiple regression. The findings of this study indicate that there is a significant association between school closure, social isolation, and the psychological well-being of gifted students. Both school closure and social isolation, when put together resulted in the poorer and lower psychological well-being of students, with school closure having a greater negative impact. Based on these findings, the study recommends the development of stronger collaborations between teachers and parents in optimising educational development of gifted children and as well as creating a safe and supportive home environment for them.