Research indicates that adolescents who experience mental health difficulties are frequently stigmatised by their peers. Stigmatisation is associated with a host of negative social and psychological effects, which impacts a young person's well-being. As a result, the development of effective anti-stigma strategies is considered a major research priority. However, in order to design effective stigma reduction strategies, researchers must be informed by an understanding of the factors that influence the expression of stigma. Although evidence suggests that empathy and social norms have a considerable effect on adolescents' social attitudes and behaviours, research has yet to examine whether these factors significantly influence adolescents' responses toward their peers with mental health difficulties. Thus, this study aims to examine whether empathy (cognitive and affective) and peer norms (descriptive and injunctive) influence adolescents' implicit and explicit stigmatising responses toward peers with mental health problems. A total of 570 (221 male and 348 female; 1 non-specified) adolescents, aged between 13 and 18 years (M = 15.51, SD = 1.13), participated in this research. Adolescents read vignettes describing male/female depressed and 'typically developing' peers. Adolescents answered questions assessing their stigmatising responses toward each target, as well as their empathic responding and normative perceptions. A sub-sample of participants (n = 173) also completed an IAT assessing their implicit stigmatising responses. Results showed that descriptive norms exerted a substantial effect on adolescents' explicit responses. Cognitive empathy, affective empathy and injunctive norms exerted more limited effects on explicit responses. No significant effects were observed for implicit stigma. Overall, empathy was found to have limited effects on adolescents' explicit and implicit stigmatising responses, which may suggest that other contextual variables moderate the effects of dispositional empathy on responding. In conclusion, these findings suggest that tackling the perception of negative descriptive norms may be an effective strategy for reducing explicit stigmatising responses among adolescents.