Introduction: Neuroticism is an important marker of vulnerability for both mental and physical disorders. Its link with multiple etiological pathways has been studied before. Inflammatory markers have been demonstrated to predict similar mental and physical disorders as neuroticism. However, currently no study has focused on the shared genetic background of neuroticism and inflammatory markers. In the present study we will focus on the phenotypic and genetic relationship between neuroticism and three commonly used inflammatory markers: C-reactive protein (CRP), fibrinogen and Immunoglobulin-G (IgG). Material and Methods: The study was conducted in 125 Dutch female twin pairs. For each participant, four different neuroticism scores were available to calculate a neuroticism composite score that was used in the statistical analyses. Blood samples for inflammatory marker determination were taken after an overnight fast. Heritabilities, phenotypic and genetic correlations were estimated using bivariate structural equation modeling. Results: Heritabilities are fair for neuroticism (0.55), CRP (0.52) and fibrinogen (0.67) and moderate for IgG (0.43). No significant phenotypic or genetic correlations were found between neuroticism and the inflammatory markers. Interaction models yielded no moderation of the genetic and environmental pathways in the regulation of inflammatory markers by neuroticism. Conclusion: Substantial heritabilities were observed for all variables. No evidence was found for significant shared (or moderation of) genetic or environmental pathways underlying neuroticism and inflammatory status.