Couples' health and health behaviors are intertwined, where the health of one partner can influence the health of the other but the biologic underpinnings are not known. We examined the associations between relational health and markers of inflammation and insulin resistance in couples coping with breast or prostate cancer. Participants (90 cancer survivor-spouse dyads) completed self-report measures of relational health including Dyadic Adjustment Scale-7 (relationship quality), Dyadic Coping Inventory (communication), and shared physical activity, as well as Community Health Activities Model Program for Seniors (individual physical activity). Inflammation (C-reactive protein (CRP)) and homeostasis model assessment of insulin resistance (HOMA-IR) were measured in serum samples. Structural equation modeling including demographic and clinical covariate controls was used to estimate separate actor and partner effects of relationship quality, communication, and physical activity on CRP and HOMA-IR. Participants were aged 63.1 ± 10.4years with an average relationship duration of 30.0 ± 1.1years. Higher survivor perceived relationship quality was associated with lower spouse CRP (b = - 0.07; 95%CI: - 0.13, - 0.01), whereas higher spouse perceived relationship quality was associated with lower survivor HOMA-IR (b = - 0.07; 95%CI: - 0.13, - 0.03). There were no other significant actor or partner effects observed. Among cancer survivor-spouse dyads, how one member of the couple perceives the quality of the relationship impacts disease biomarkers in the other, providing preliminary evidence for biological linkage between relational health and chronic disease risk. Relationship quality may positively influence biomarkers of inflammation and insulin resistance in couples coping with breast and prostate cancer. Dyadic approaches to optimize survivorship health may be warranted. ClinicalTrials.gov NCT03630354, 08/14/2018; Open Science Framework ( https://bit.ly/3S4rUtJ ).