To verify the portrait of increased inflammatory signaling that emerged from functional genomic analyses, we assayed circulating levels of C-reactive protein (CRP) in blood samples obtained during study years 2, 3, and 4. In mixed effect linear model analyses (Year × Loneliness factorial design), high-lonely individuals showed average CRP values approximately twice those of low-lonely participants (mean = 1.33 ± 0.22 mg/l versus 0.65 ± 0.22; Loneliness main effect, p = 0.0014).