Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) Introduction: Cognitive performance and inflammation are altered in people with chronic low back pain (CLBP). Yet, the magnitude of these changes has been unclear because of the potential influence of opioid analgesics. Objectives: This cross-sectional pilot study aimed to explore whether patients with CLBP receiving long-term opioid analgesics differed from patients not taking opioids on measures of cognitive performance and plasma cytokine concentrations. Methods: Patients with CLBP who were either taking (N 5 18) or not taking (N 5 22) opioids daily for 3 or more months were recruited from a tertiary care private hospital and compared with healthy adults (N 5 20). All groups were administered validated questionnaires to assess depression, anxiety, and stress; a cognitive test of memory, attention, and executive function; and a peripheral blood draw to measure proinflammatory (IL-1b, IL-2, IL-8, IL-12p70, TNF-a, and IFN-g), anti-inflammatory (IL-4, IL-10, and IL-13), and pleiotropic (IL-6) cytokine concentrations. Patients also completed pain-specific questionnaires. Results: Patients receiving opioid analgesics performed significantly (P, 0.05) worse in attention and had significantly (P, 0.05) lower pain self-efficacy beliefs than those patients not taking opioids. Patient groups did not differ in mean pain severity or pain interference scores, tests of memory and executive function, and mean plasma cytokine concentrations, despite long-term opioid analgesics. Conclusion: Patients receiving long-term opioid analgesics for CLBP have minor differences when compared with patients not taking opioids. This has important clinical implications when considering long-term treatment for patients with CLBP.