Social rejection is a critical risk factor for adolescents’ mental health, yet adolescents differ markedly in how emotionally they respond to everyday rejection. This preregistered study examined adolescents’ emotional responses to everyday social rejection, and whether these responses are moderated by neurodevelopmental changes across childhood and cognitive emotion regulation (CER). Dutch adolescents (N=195, aged 15–17) completed a 17-day Experience Sampling Method (ESM) protocol with six assessments per day, reporting perceived social rejection and momentary affect (loneliness, irritation, cheerfulness) across offline and online social contexts. Longitudinal changes in dorsolateral prefrontal cortex (DLPFC) activation across childhood and CER were assessed as moderators of within-person rejection–affect associations. Daily social rejection was prevalent but typically low in intensity. When adolescents experienced more rejection than usual, they reported increased loneliness and irritation and decreased cheerfulness. These associations were stronger for offline than online rejection and were amplified when rejection occurred across both contexts. Importantly, maladaptive CER strengthened rejection-related loneliness, whereas stronger developmental increases in DLPFC activation across childhood attenuated adolescents’ loneliness responses to rejection. Our findings show that the emotional impact of everyday social rejection reflects individual differences in neurodevelopmental maturation and highlight emotion regulation as a potential mechanism underlying adolescents’ social sensitivity.