Oxaliplatin is a highly neurotoxic chemotherapeutic agent routinely used for the treatment of colorectal cancer. Recent data suggest that oxaliplatin-induced peripheral neuropathy may be long-lasting; however, the effects of persistent neuropathy on colorectal cancer survivors’ physical and emotional well-being are not well understood. This cross sectional, descriptive study included persons who had received oxaliplatin-based chemotherapy for treatment of colorectal cancer at Moffitt Cancer Center between 2003 and 2010. Questionnaires including the Chemotherapy-Induced Peripheral Neuropathy Assessment Tool, Center for Epidemiological Studies Depression Scale (CES-D), Insomnia Severity Index, Medical Outcomes Study Short Form 36, and a demographic survey were administered. Pearson’s correlations and linear regression analyses were used to examine relationships between neuropathy and depressive symptoms, sleep quality, and health-related quality of life (HRQOL). Eighty-nine percent of participants reported at least one symptom of peripheral neuropathy with a mean of 3.8 (±2.4) neuropathic symptoms. Depressive symptoms on the CES-D were significantly associated with more severe peripheral neuropathy(r = 0.38, p = 0.0001) and interference with activities (r = 0.59, p < 0.0001). Higher degrees of sleep disturbance on the Insomnia Severity Index (ISI) were significantly associated with more severe peripheral neuropathy (r = 0.35, p = 0.0004) and interference with activities(r = 0.52, p < 0.0001). HRQOL was significantly associated with peripheral neuropathy and interference with activities.