Throughout the 1990s, many villagers in rural China were infected with HIV through commercial plasma/blood donation. These former plasma/blood donors (FPDs) experienced many HIV-related stressors. This study tested a cognitive appraisal model of stress and coping in a sample of HIV-positive adult FPDs. Participants (N = 207) from multiple villages completed a battery of questionnaires assessing HIV-related stress, HIV symptoms, cognitive appraisal, coping behaviors, and psychological distress. Participants reported high levels of HIV-related stress, depression, and anxiety. In a structural equation model, greater HIV-related stress, HIV symptoms, and threat appraisal were directly associated with psychological distress. HIV-related stress was also indirectly associated with psychological distress through threat appraisal. In a second model, coping was found to mediate the relationship between challenge appraisal and psychological distress. Results support the utility of cognitive appraisal theory. Stress management interventions targeting HIV-positive FPDs in China are indicated.