The growing evidence linking social connectedness and chronic diseases such as cancer calls for a better understanding of the underlying biophysiological mechanisms. This study assessed the associations between social network ties and multiple measures of inflammation in a nationally representative sample of adults with a history of cancer (N = 1,075) from the National Health and Nutrition Examination Survey III (1988–94). Individuals with lower social network index (SNI) scores showed significantly greater inflammation marked by C-reactive protein and fibrinogen, adjusting for age and sex. Compared to fully socially integrated individuals (SNI 4), those who were more socially isolated or had a SNI score of 3 or less exhibited = increasingly elevated inflammation burdens. Specifically, the age- and sex-adjusted odds ratios (95%CI) for SNIs of 3, 2, and 0–1 were 1.49 (1.08, 2.06), 1.69 (1.21, 2.36), and 2.35 (1.62, 3.40), respectively (p < .001). Adjusting for other covariates attenuated these associations. The SNI gradients in the risks of inflammation were particularly salient for the lower socioeconomic status groups and remained significant after adjusting for other social, health behavioral, and illness factors. This study provided initial insights into the immunological pathways by which social connections are related to morbidity and mortality outcomes of cancer in particular and aging-related diseases in general.