The error-related negativity (ERN/Ne) and error positivity (Pe) have been associated with error detection and response monitoring. More recently, heart rate (HR) and skin conductance (SC) have also been shown to be sensitive to the internal detection of errors. An enhanced ERN has consistently been observed in anxious subjects and there is some suggestion that the ERN is related to general negative affective experience (NA). The ERN has been source localized to the anterior cingulate cortex (ACC)—a structure implicated in the regulation of affective, response selection, and autonomic resources. Thus, the findings that autonomic measures and affective distress are related to response monitoring are consistent with ACC function. In the present experiment, we sought to evaluate more comprehensively the relationship between self-reported negative affect and error-related physiology in a between-groups design. Results indicate that high NA was associated with significantly greater ERN and error-related SCR, and smaller Pe. These results are discussed in terms of ACC function, psychopathology, and response monitoring.