Keratinocyte apoptosis is a key pathogenetic mechanism in atopic dermatitis (AD). Fas and Fas ligand (FasL) interaction is an important pathway to induce apoptosis. However, the relationship between early life soluble FasL (sFasL) and AD still is not clear. This study was designed to evaluate if sFasL is associated with the development of AD in children. We performed a nested case-control study within a prospective Taiwan birth-panel cohort study. Umbilical cord blood and maternal plasma samples were gathered at birth. During follow-up, using the International Study of Asthma and Allergies in Childhood questionnaires, we identified 40 AD cases, which we matched to 80 unaffected controls chosen from this cohort. The concentrations of sFasL and immunoglobulin E in plasma were determined by enzyme-linked immunosorbent assay. The relationship of sFasL levels and AD was estimated by mix model. Receiver operating characteristic (ROC) curves were generated to see how well sFasL could predict AD. Cord blood sFasL levels were significantly higher in the AD patients than in the controls (p = 0.003). The concentration of sFasL in the cord blood was higher than in the maternal blood (p < 0.001). There also existed a correlation between the concentration of sFasL in the maternal blood and the cord blood (r = 0.23; p = 0.01). The subjective severity of AD was positively correlated with sFasL levels (r = 0.34; p = 0.02). Cold blood sFasL may be a biomarker in detecting pediatric AD (area under the ROC curve = 0.64). Our results showed a relation between cord blood sFasL and the development of AD in children.