The experience of cancer elicits not only turmoil but also resilience in the family, which has been related to psychological adjustment and physical health of family caregivers. The biological pathways linking family cancer caregiving to health, however, remain poorly understood. This study examined the extent to which psychological risk and resilience factors related to a proinflammatory gene expression profile (conserved transcriptional response to adversity, or CTRA) among caregivers during the first-year postdiagnosis of a patient with colorectal cancer. A total of 41 caregivers (mean age = 54 years, 74% female, 40% Hispanic) provided psychological data and peripheral blood samples around 4 and 12 months after diagnosis. Mixed regression models controlling for demographic and biometric factors were used to test the associations of caregiver CTRA gene expression with caregiving stress, loneliness, and lack of social support (risk factors), as well as benefit finding and meaning (resilience factors). When individually tested, all but benefit finding were significantly related to CTRA (R2 ≥ 0.112, p < .045). When adjusted for other factors in either the risk or resilience group, loneliness, social support, and meaning effects remained significant (R2 ≥ 0.120, p < .041). When all study factors were simultaneously adjusted (R2 = 0.139), only loneliness remained significant (p = .034). Findings suggest that caregiving-related transcriptional effects seem to be most pronounced when caregivers experience low social support and loneliness, as well as little meaning or purpose in their caregiving. These findings suggest that the development of new intervention strategies that prioritize reductions in caregiver loneliness may favorably impact biological mechanisms related to caregiver health.