The study explored the roles of attitude towards science and mathematics, and knowledge of COVID-19 pandemic in prediction of secondary school students’ COVID-19 vaccine acceptance in Nsukka Education Zone, Enugu State Nigeria. The study employed a correlation survey research design. The population of the study comprised 3,789 secondary school three (SS3) students in the zone. The sample size of the study was 350 students selected through multi-stage sampling procedure. Three hypotheses, tested at 0.05 level of significance guided the study. Three adapted instruments, (1) student’ attitude towards science and mathematics questionnaire (ATSMQ), (2) students’ knowledge of COVID-19 pandemic questionnaire (KCPQ), and (3) students’ COVID-19 vaccine acceptance questionnaires (CVAQ), were used for collection of data. The estimate of internal consistency of the instruments were determined using Cronbach’s alpha. The obtained reliability coefficients of ATSMQ, KCPQ, and CVAQ were 0.78, 0.89, and 0.91, respectively. Simple and multiple regression analysis were performed to test the hypotheses at 0.05 level of significance using R, R2, and regression analysis of variance (ANOVA). The findings revealed, among others, that attitude towards science and mathematics and knowledge of COVID-19 pandemic were significant predictors of COVID-19 vaccine acceptance. It is recommended, among others, that teachers, government at all levels, non-governmental organizations, and members of the task force on COVID-19 prevention, should carry out aggressive campaign to increase knowledge of COVID-19 pandemic among the students.
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