Stress or negative mood often promotes energy intake and overeating. Since the serotonin transporter-linked polymorphic region (5-HTTLPR) is found to mediate stress vulnerability as well as to influence energy intake, this gene may also influence the negative effects of stress exposure on overeating. Moreover, since stress proneness also reflects cognitive stress vulnerability - as often defined by trait neuroticism - this may additionally predispose for stress-induced overeating. In the present study it was investigated whether the 5-HTTLPR genotype interacted with neuroticism on changes in mood, appetite and energy intake following exposure to a real-life academic examination stressor. In a balanced-experimental design, homozygous S-allele and L-allele carriers (N = 94) with the lowest and highest neuroticism scores were selected from a large database of 5-HTTLPR genotyped students. Mood, appetite and energy intake were measured before and after a 2-hour academic examination and compared with a control day. Examination influenced appetite for particular sweet snacks differently depending on 5-HTTLPR genotype and neuroticism. S/S compared with L/L subjects reported greater examination stress, and this was accompanied by a more profound post-stress increase in appetite for sweet snacks. Data also revealed a 5-HTTLPR genotype by trait neuroticism interaction on energy intake, regardless of examination. These results consolidate previous assumptions of 5-HTTLPR involvement in stress vulnerability and suggest 5-HTTLPR and neuroticism may influence stress-induced overeating depending on the type of food available. These findings furthermore link previous findings of increased risk for weight gain in S/S-allele carriers, particularly with high scores on trait neuroticism, to increased energy intake.