This study was designed to investigate whether dexketoprofen added to perineuraly or subcutaneously alters the effects of levobupivacaine in a rat model of sciatic nerve blockade. Thirty-six rats received unilateral sciatic nerve blocks along with a subcutaneous injection by a blinded investigator assigned at random. Combinations were as follows: Group 1 (sham) perineural and subcutaneous saline; Group 2, perineural levobupivacaine alone and subcutaneous saline; Group 3, perineural levobupivacaine plus dexketoprofen and subcutaneous saline; Group 4, perineural levobupivacaine and subcutaneous dexketoprofen; Group 5, perineural dexketoprofen and subcutaneous saline; and Group 6, perineural saline and subcutaneous dexketoprofen. The levobupivacaine concentration was fixed at 0.05%, and the dose of dexketoprofen was 1 mg kg−1. Sensory analgesia was assessed by paw withdrawal latency to a thermal stimulus every 30 min. The unblocked paw served as the control for the assessment of systemic, centrally mediated analgesia. Perineural and subcutaneous dexketoprofen coadministered with perineural levobupivacaine did not enhance the duration of sensory blockade when compared with levobupivacaine alone. There were significant differences between the operative and control paws for time points 30–90 min in the perineural levobupivacaine alone, levobupivacaine + dexketoprofen and subcutaneous dexketoprofen added levobupivacaine group. Significant differences were not determined between the levobupivacaine alone group and dexketoprofen added groups in operative paw. The effects of dexketoprofen are unknown for perineural administration. There is no significant difference between the analgesic effects of peripheral nerve blocks using levobupivacaine alone and plus subcutaneous or perineural dexketoprofen.