We assessed effectiveness of Fascial Manipulation (FM) in reducing densification thickness and associated acute pain in normal humans. Fascial densifications were identified using palpation and measured with diagnostic ultrasound within self-reported painful somatic regions. Pain intensity ratings were obtained in response to deep palpation of the self-reported painful somatic region before and after a brief FM intervention. Brief FM resulted in reduced densification thickness as well pain intensity. Sex differences were found neither in densification thickness nor pain intensity at any time point. However, a statistically significant positive correlation between densification thickness and pain intensity was observed in females but not males at both pre-FM and post-FM time points. As such, FM may be an effective therapeutic approach for acute pain associated with fascial densifications. While males and females exhibited comparable densification thickness and pain intensity levels at both pre-FM and post-FM time points, only females showed a statistically significant relationship between pain and densification, suggesting that females may be better able to perceive subtle differences in the magnitude of noxious sensory input.