Objective: In 1995, the Centers for Disease Control and Prevention defined chronic multisymptom illness (CMI), a symptom complex in deployed veterans (DVs) of the 1991 Gulf War 1. The specific aim of this work is to determine the prevalence of CMI in spouses of DV and nondeployed veterans (NDVs) and whether veteran CMI is associated with spouse CMI, and to describe the physical and psychological profile of spouses with CMI. Materials and Methods: To determine whether veteran CMI was associated with CMI in their spouses, we used retrospective data from the “National Health Survey of Gulf War Veterans and Their Families.” Cross-sectional data were collected from spouses of veterans enrolled in the study, including those of 482 DVs and 532 NDVs who participated in an in-person examination between 1999 and 2001. In addition to a physical examination, this study evaluated healthrelated quality of life (Medical Outcomes Study Short-Form 36, SF-36), psychological symptoms, and post-traumatic stress disorder (PTSD) status, and measured a variety of common laboratory tests. Statistical analyses included Fisher’s Exact Test (or Mantel–Haenszel χ2 test for linear trend) as well as odds ratios (ODs) and 95% confidence intervals (CIs) for categorical data. For continuous outcomes, two-sample t-tests were used to compare mean responses among spouses of DV and NDV with and without CMI, and between spouses of DV and NDV with CMI only. Logistic or linear regression models were developed for multiple-covariate analysis to assess if any of the associations we found in the unadjusted analyses would change. The project was approved by the Hines Cooperative Studies Program Human Rights Committee, the Institutional Review Boards at each participating site, and the Brockton VAMC. Results: The prevalence of CMI in spouses was 19.5% (DV) and 17.3% (NDV) (odds ratio [OR]: 1.16; 95% confidence interval [CI]: 0.84, 1.59). Spouses were more likely to have CMI if their veteran partner had CMI (OR: 1.49; 95% CI: 1.01, 2.19) or PTSD (OR: 1.84; 95% CI: 1.01, 3.37). Deployment was not a predictor of CMI. Spouses with CMI reported poorer SF-36 physical and mental component scores; worse symptoms of depression, anxiety, and post-traumatic stress; and a higher percentage had probable PTSD, more nonroutine clinic visits, more hospitalization, more prescription medications, and more psychotropic medication use compared with spouses without CMI regardless of the deployment status of their veteran spouses. Conclusion: Spouses of veterans with CMI report worse physical and mental functioning than spouses of veterans without CMI, regardless of the veteran’s deployment status. Strengths of the study include that all participants were selected independently of veteran medical or psychiatric illness, and all underwent comprehensive health assessments. Weaknesses of the study include that data were not collected blindly, and that we made minor modifications of the Centers for Disease Control and Prevention diagnosis, such as defining fatigue and musculoskeletal pain more restrictively. The impact of veteran CMI on their spouse’s health is likely to be significant in terms of medical cost and morbidity. Efforts to reduce the impact of CMI in the future should include identifying soldiers who are more vulnerable, such as those with prior GWI or PTSD.