Contact isolation of patients with multi-drug-resistant organisms (MDROs) is an essential element of infection prevention strategies in hospitals worldwide. However, this practice may be associated with adverse side effects on patients' health and well-being. This study was the first to assess mental health and well-being variables among isolated patients compared with non-isolated control patients in a German cohort. We conducted a matched case–control study among N = 267 patients admitted to a tertiary care teaching hospital in Germany. Their levels of anxiety, depression, loneliness, and dissatisfaction with their hospital experience were assessed using a questionnaire. Additionally, among isolated patients, it was evaluated how well they felt informed about their MDRO status. In our cohort, patients under contact isolation were significantly more dissatisfied than non-isolated control patients but did not show higher levels of anxiety, depression, and loneliness. A large proportion of patients felt insufficiently informed about their MDRO status. This lack of information was the strongest predictor of dissatisfaction among isolated patients. These findings underline the importance of adequate patient communication. It is essential for patients' well-being to receive timely, relevant, and understandable information about the background and consequences of their infection or colonisation with MDROs.