The burden of post-stroke cognitive impairment, as well as affective disorders, remains persistently high. With improved stroke survival rates and increasing life expectancy, there is a need for effective interventions to facilitate remediation of neurocognitive impairments and post-stroke mood disorders. To investigate the effects of Therapeutic Instrumental Music Performance (TIMP) training with and without Motor Imagery on cognitive functioning and affective responding in chronic post-stroke individuals. Thirty chronic post-stroke, community-dwelling participants were randomized to one of three experimental arms: (1) 45 minutes of active TIMP, (2) 30 minutes of active TIMP followed by 15 minutes of metronome-cued motor imagery (TIMP+cMI), (3) 30 minutes of active TIMP followed by 15 minutes of motor imagery without cues (TIMP+MI). Training took place three times a week for three weeks, using a selection of acoustic and electronic instruments. Assessments, administered at two baselines and post-training, included the Trail Making Test (TMT) - Part B to assess mental flexibility, the Digit Span Test (DST) to determine short-term memory capacity, the Multiple Affect Adjective Checklist - Revised (MAACL-R) to ascertain current affective state, and the General Self-Efficacy Scale (GSE) to assess perceived self-efficacy. The Self-Assessment Maniqin (SAM) was also administered prior to and following each training session. Thirty participants completed the protocol, ten per arm [14 women; mean age = 55.9; mean time post-stroke = 66.9 months]. There were no statistically significant differences between pooled group baseline measures. The TIMP+MI group showed a statistically significant decrease in time from pre-test 2 to post-test on the TMT. The TIMP group showed a significant increase on MAACL sensation seeking scores, as well as on the Valence and Dominance portions of the SAM; TIMP+cMI showed respective increases and decreases in positive and negative affect on the MAACL, and increases on the Valence, Dominance, and Arousal portions of the SAM. No statistically significant association between cognitive and affective measures was obtained. The mental flexibility aspect of executive functioning appears to be enhanced by therapeutic instrumental music training in conjunction with motor imagery, possibly due to multisensory integration and consolidation of representations through motor imagery rehearsal following active practice. Active training using musical instruments appears to have a positive impact on affective responding; however, these changes occurred independently of improvements to cognition.