Early maternal separation has profound effects on nociception in rats. Cross-fostering is a standard husbandry procedure used by some commercial breeders. This study aimed to determine if cross-fostering altered nociception and the analgesic efficacy of buprenorphine and morphine. At seven and nine weeks of age, an elevated plus maze was used to assess anxiety and Hargreaves apparatus was used to measure thermal nociception at two intensities in cross-fostered and naturally-reared rats. At 10 weeks of age these rats were assigned to one of three treatment groups: saline, buprenorphine or morphine. The Hargreaves apparatus was used to evaluate the effect of analgesics on nociception. Differences were observed in nociception between the cross-fostered and naturally-reared rats at both intensities. At the lower intensity no significant differences were seen between the cross-fostered and naturally-reared rats post-administration of an analgesic. At the higher intensity significant differences were apparent. Morphine was less effective in inducing analgesia to thermal stimuli in cross-fostered rats compared with naturally-reared rats, whereas the opposite was found with buprenorphine which had a more pronounced analgesic effect in the cross-fostered rats. No significant differences in performance on an elevated plus maze were demonstrated between the cross-fostered and naturally-reared rats.