The present research examined comparison targets and comparison dimensions among two Spanish samples of individuals facing serious illnesses and diseases. In Study 1, 90 older patients (mean age 66.36) with various age-related diseases, particularly cardiovascular diseases and diabetes, indicated that they compared themselves most often with others with the same disease, next with others with another disease and least with people without health problems. They compared themselves more often on their mental state, symptoms and physical activities than on their social activities. Social comparison orientation (SCO) as an individual difference characteristic was associated with more frequent comparisons with particularly similar targets, and with more frequent comparisons of one's symptoms and physical activities. Neuroticism was correlated only with more comparisons of one's symptoms. Study 2 was conducted in a sample of 70 relatively young patients (mean age 43.97) with spinal cord injury (SCI). Overall, they compared themselves more often with others than the participants in Study 1, and they compared themselves to a similar extent with people with SCI as with people with another disease and with people without health problems. While they felt on average better off than people with other diseases and other people with SCI, people with SCI felt on average worse off than people without health problems. They compared themselves more often on physical activities than on any other dimension. Higher levels of stress and uncertainty were associated with more frequent comparisons with people without SCI, and with more frequent comparisons of one's mental state, one's symptoms and one's future perspectives. The discussion focuses on the theoretical relevance of the results for social comparison theory, and on the practical relevance of the findings for interventions.