Aim: Several skin disorder symptoms may appear in infants, each resulting from a different inflammatory response. In this study, we investigated the relationship between skin cytokine levels and skin symptoms in newborns. Methods: This cross‐sectional study was conducted in Tokyo and Oita, two Japanese cities. The participants were healthy, 1‐month‐old infants and their parents. Symptoms including erythema, papules, dryness, and exudate/yellow scaling on infant faces were evaluated as outcomes. Cytokine levels (interleukin [IL]‐4, IL‐6, IL‐8, and IL‐17) were measured by skin blotting. A multilevel analysis using a mixed‐effects model was conducted to account for regional differences. Results: A total of 231 infants (119 from Tokyo and 112 from Oita) participated in this study. Erythema, papules, dryness, and exudate/yellow scaling were present in 59 (25.5%), 133 (57.6%), 37 (16.0%), and 16 (6.9%) of the infants, respectively. In terms of the associations between symptoms and cytokines, there was a significant association between papules and IL‐8 positivity (adjusted odds ratio [AOR]: 1.94, 95% confidence interval [CI] 1.09–3.47) even after adjustment for differences in barrier function, area, and skin care. Conclusions: This study demonstrated that cytokines were linked to skin conditions, even after accounting for regional differences and genetic factors. This suggests that different symptoms point to the involvement of various cytokines in skin conditions in neonates, with mechanisms varying based on the symptoms. These findings could aid in developing specific preventive strategies in the future. [ABSTRACT FROM AUTHOR]