Our study is guided by Beck’s cognitive stress-vulnerability model of depression. We examined the associations between perceived everyday discrimination (PED) and TNF-⍺, an inflammatory biomarker associated with risk for severe illness, through the negative cognitive triad (NCT; negative thoughts about the self, world, and future) and depressive symptoms in adolescents. We utilized a sample of 99 adolescents (36.4% female; ages 13–16, M = 14.10, SD = 0.52) in our cross-sectional study. We used PROCESS and AMOS to compute regressions and direct, indirect, and total effects of PED, NCT aspects and depressive symptoms on TNF-⍺. Negative views of the self and world mediated between PED and depressive symptoms and that negative views of the self and future mediated between PED and TNF-⍺. In conclusion, Beck’s theory can be expanded to physical health providing directions for addressing mental and physical health simultaneously by restructuring adolescents’ negative view of the self.