•High clinical pain intensity is not the sole determinant of opioid craving.•Opioid withdrawal symptoms contribute to opioid craving in patients with pain.•Opioid withdrawal symptoms contribute to higher negative affect and catastrophizing.•Psychological distress mediates the link between withdrawal symptoms and craving. Research has shown that opioid craving is one of the strongest determinants of opioid misuse in patients with chronic pain. To date, however, little is known on the factors that contribute to opioid craving in these patients. It is possible that patients’ physical dependence to opioids, manifested by opioid withdrawal symptoms in between daily opioid doses, contribute to opioid craving. Physical dependence symptoms might also lead to psychological distress, which in turn might contribute to opioid craving. The first objective of this study was to examine the day-to-day association between opioid withdrawal symptoms and opioid craving among patients with chronic pain. We also examined whether negative affect and catastrophic thinking mediated this association. In this longitudinal study, chronic pain patients (n = 79) prescribed short-acting opioids completed daily diaries for 14 consecutive days. Diaries assessed a host of pain, psychological, and opioid-related variables. Day-to-day elevations in opioid withdrawal symptoms were associated with heightened opioid craving (p < .001). Results of a multilevel mediation analysis revealed that this association was mediated by patients’ daily levels of negative affect and catastrophizing (p < .001). Our study provides valuable new insights into our understanding of factors that may contribute to prescription opioid craving among patients with chronic pain.