Side effects from HIV treatments impact quality of life (QOL) and adherence to care, and influence decisions about health care. The purposes of this study are to describe the development of a measure of coping with HIV treatment side effects, the SECope, and to provide support for the reliability and validity of the measure. Based in Stress and Coping Theory, the 20-item measure assesses strategies for coping with HIV treatment side effects, and includes scales of Positive Emotion Focused Coping, Social Support Seeking, Nonadherence, Information Seeking, and Taking Side Effect Medications. The factor structure was supported by exploratory and confirmatory factor analyses with two samples of HIV+ individuals on treatment (Ns = 173 and 233). The SECope has demonstrated reliability (internal consistency and test-retest), and its validity is supported through construct and criterion-referenced analyses. Nonadherence as a strategy for coping with side effects was associated with poorer provider relations, lower treatment knowledge, and higher beliefs of treatment effectiveness. Findings have the potential to inform investigations and interventions in the context of treatment of HIV disease and other medical conditions.