•FGF2 levels are lower in clinic-referred compared with non-referred children•FGF2 levels show a negative factor loading on Anxiety/Depression latent variable•FGF2 levels over six months show good stability in the non-referred children•Peripheral FGF2 levels play a role in anxiety and depression in children•Results lay the foundation for further research on the FGF2 system as a potential biomarker for pediatric anxiety and depression Research links fibroblast growth factor 2 (FGF2) to anxiety and depression in rodents and human adults. Our study is the first to examine FGF2 levels in a pediatric population. We assayed serum FGF2 in 163 children with a broad range of anxiety and depressive symptoms; 111 were clinic-referred anxious and depressed children; 52 were non-referred children. We examined associations between FGF2 and anxiety and depression symptoms, and between each of the three facets of behavioral activation (Reward-Responsiveness, Drive, Fun-Seeking) and behavioral avoidance. We used confirmatory factor analysis (CFA) to determine the relative contribution of anxiety and depression indicators and of FGF2 to a latent variable of Anxiety/Depression. We also examined stability of FGF2 levels. FGF2 levels in clinic-referred children were significantly lower compared with non-referred children. Bivariate correlations and CFA showed negative associations between FGF2 and anxiety, depression and behavioral avoidance. FGF2 levels were positively correlated with the Reward-Responsiveness facet of behavioral activation, implicated in depression. FGF2 levels were stable over six months. We did not have data on behavioral avoidance and stability of FGF2 in the entire sample. Our results implicate FGF2 in anxiety and depression in children, providing an important first step in showing FGF2 may serve as a stable biomarker for these prevalent and impairing problems.