Background and aims Opioid consumption has increased dramatically in patients with chronic non-cancer pain (CNCP), but long-term consequences are still unclear. The aim of this study is to investigate the effects of long-term opioid treatment on pain, cognition, mood, sleep and quality of life in CNCP patients. Methods In this cross-sectional pilot study, two groups of patients with CNCP treated in a multidisciplinary pain center were selected: (1) opioid group: ≥30 mg morphine equivalent/day for >4 weeks, and (2) control group: no opioid consumption for >4 weeks. Socio-demographic data, alcohol consumption, smoking habits and body mass index (BMI) were registered and pain (brief pain inventory), mood (Hospital Anxiety and Depression Scale), sleep (Pittsburgh Sleep Quality Index) and quality of life (RAND 36-Item Health Survey) were assessed. Continuous Reaction Time and the Digit Span Test were used to evaluate cognitive function. Data was analyzed with a Fisher's exact test and Wilcoxon two-sample test. Results Forty-two patients with CNCP were included (21 in each group). No differences regarding socio-demographics, smoking/alcohol habits and duration, type, or intensity of pain were found. More patients in the opioid group had significantly higher BMI (62% above BMI 25 vs. 33.3%, p = 0.042). Consequently, the subsequent data analyses were controlled for BMI. The two groups did not differ in pain, cognition, anxiety, depression, sleep or quality of life but both showed lower values than the normal standards. Further, the opioid group presented a tendency to lower ratings regarding pain and social function and performed below the normal cut off in the continuous reaction time. Conclusions No significant differences between the two groups were found regarding any of the above-mentioned variables. Interestingly, the patients assessed, regardless of taking opioids or not, could be classified with moderate pain intensity, anxiety and low quality of sleep and life compared to norm standards. Implications The findings of this pilot study suggested that long-term opioid treatment may influence pain and quality of life among CNCP patients. A larger cohort is needed to verify these findings.