The purpose of this study was to evaluate clinically the effects of pre-treatments with a 35% hydroxyethyl metacrylate/5% glutaraldehyde dentine desensitizer (Gluma Desensitizer) and a 2% chlorexidine-based cavity disinfectant (Cav-Clean) on postoperative sensitivity. Three premolar teeth with no pain symptoms were selected from each one of 17 patients, totalling 51 teeth, for which Class II restoration using a composite was indicated. Each one of the three premolar teeth of the same patient was submitted to a different treatment. After acid etching, only a dental adhesive was applied to the first tooth, which served as the control. Gluma Desensitizer dentinal desensitizer was applied to the second premolar tooth prior to applying the dental adhesive. Cav-Clean cavity disinfectant was used on the third premolar tooth before applying the dental adhesive. Only one tooth was restored per session, and all premolar teeth were restored with a condensable composite, according to current restoration technique guidelines. Sensitivity to different stimuli (cold, heat, sweet and dental floss) was assessed on Day 1, Day 4 and Day 7 by questionnaire following restorative procedures. The results of this clinical research showed that, as far as the investigated stimuli and postoperative course are concerned, there was no statistically significant difference in the three different treatments (P>0.05). Postoperative sensitivity resulting from Class II restorations using composite resin cannot be completely eliminated with the prior use of a dentinal desensitizer or a cavity disinfectant. In day-to-day clinical treatment, postoperative sensitivity may possibly be related to the technique employed.