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Different studies have shown that the use of olfactory stimuli during painful medical procedures reduces infants' response to pain. The main purpose of the current study was to investigate the effect of breast milk odor and vanilla odor on premature infants' vital signs including heart rate and blood oxygen saturation during and after venipuncture. Methods: A total of 135 preterm infants were randomly selected and divided into three groups of control, vanilla odor, and breast milk odor. Infants in the breast milk group and the vanilla group were exposed to breast milk odor and vanilla odor from 5 minutes prior to sampling until 30 seconds after sampling. Results: The results showed that breast milk odor has a significant effect on the changes of neonatal heart rate and blood oxygen saturation during and after venipuncture and decreased the variability of premature infants' heart rate and blood oxygen saturation. Vanilla odor has no significant effect on premature infants' heart rate and blood oxygen saturation. Conclusion: Breast milk odor can decrease the variability of premature infants' heart rate and blood oxygen saturation during and after venipuncture.