This study evaluates the construct validity and internal consistency of a Chronic Illness-Related Stress Inventory (CRSI) for primary care Chinese patients and studies the relationship between chronic illness-related stress and sociodemographic characteristics and indices of disease severity. A total of 301 patients were interviewed using a structured questionnaire. The responses to the CRSI were divided into a frequency scale and a severity scale. Six factors including physical integrity and discomfort, psychosocial function and economic burdens, self-fulfillment and daily life, sexual function, self-esteem, and diet limitations were obtained for each CRSI scale. Except for the last factor, all other factors and the scale as a whole for both scales have a Cronbach α of >0.90. The results of the convergent and discriminant validity analysis were promising. In addition, chronic illness-related stress was related to insurance status and the self-perceived severity of disease.