Given the influence of systemic blood pressure on pulpal blood flow, anxiolytics prescribed may alter the pulpal blood flow along with the local anesthetic solution containing a vasoconstrictor. This study evaluated the impact of preoperative anxiolytics and vasoconstrictors in local anesthetic agents on pulpal oxygen saturation. Methods. Thirty anxious young healthy individuals with a mean age of 24 years were randomly selected using the Corah's Dental Anxiety Scale (DAS). After checking the vital signs the initial pulpal oxygen saturation (initial SpO2) was measured using a pulse oximeter. Oral midzolam was administered at a dose of 7.5 mg. After 30 min, the vital signs were monitored and the pulpal oxygen saturation (anxiolytic SpO2) was measured. A total of 1.5 mL of 2% lidocaine with 1:200000 epinephrine was administered as buccal infiltration anesthesia and 10 min the final pulpal oxygen saturation (L.A SpO2) was measured. Results. The mean initial (SpO2) was 96.37% which significantly decreased to 90.76% (SpO2) after the administration of the anxiolytic agent. This drop was later accentuated to 85.17% (SpO2) after administration of local anesthetic solution. Statistical significance was set at P<0.0001. Conclusion. High concentrations of irritants may permeate dentin due to a considerable decrease in the pulpal blood flow from crown or cavity preparation. Therefore, maintaining optimal blood flow during restorative procedures may prevent pulpal injury.