<p>High negative affect and low positive affect form a generalized vulnerability to emotional disorders, including health anxiety. The purpose of this study was to examine which specific vulnerabilities of anxiety sensitivity, somatosensory amplification, intolerance of uncertainty, and metacognitions about health anxiety mediate the pathways from negative affect and positive affect to health anxiety. Undergraduates (<i>N</i> = 564) completed self-report questionnaires. Mediational analyses demonstrated that the pathway from negative affect to health anxiety was mediated by anxiety sensitivity physical concerns, somatosensory amplification, and the metacognitions that thoughts can cause illness and that thoughts about illness are uncontrollable. In particular, the pathway from negative affect to health anxiety was primarily mediated by anxiety sensitivity physical concerns and the metacognition that thoughts about illness are uncontrollable. However, the specific vulnerabilities did not mediate the pathway from positive affect to health anxiety. These findings highlight that anxiety sensitivity physical concerns and metacognitions that thoughts about illness are uncontrollable play key roles in health anxiety.</p>