Although the study of affective profiles has generated great interest in recent years, no investigations were found that analyze their relationship with school refusal. The present study identified the affective profiles arising from combining positive affect (PA) and negative affect derived from the 10-item Positive and Negative Affect Schedule for Children (PANAS-C) and determined the existence of significant differences between the found affective profiles in school refusal measures obtained from the School Refusal Assessment Scale Revised for Children (SRAS-R-C) in a sample of 1575 Spanish students (aged 8–11 years). On the one hand, cluster analyses confirmed the four affective profiles: Self-Fulfilling Profile (high PA and low NA), High Affective Profile (moderately high PA and high NA), Low Affective Profile (low PA and NA) and Self-Destructive Profile (low PA and high NA). On the other hand, post hoc contrasts showed that students from the Self-Destructive Profile scored significantly higher in the first three factors and the total score of the SRAS-R-C in comparison with the rest of profiles. Conversely, the Self-Fulfilling Profile obtained significantly higher scores in the fourth factor of the SRAS-R-C in comparison with the Low Affective and Self-Destructive Profiles. Due to the fact that the first three factors of the SRAS-R-C have been related with the presence of anxious or depressive symptomatology, the results of this manuscript confirmed that the Self-Destructive Profile is the most maladaptive affective profile and it is important to control and reduce the negative emotional reactions expressed by students in school situations.