Abstract The myoma pseudocapsule (MP) is a fibro-vascular network rich of neurotransmitters, as a neurovascular bundle, surrounding fibroid and separating myoma from myometrium. We investigated the distribution of the opioid neuropeptides, as enkephalin (ENK) and oxytocin (OXT), in the nerve fibers within MP and their possible influence in human reproduction in 57 women. An histological and immunofluorescent staining of OXT and ENK was performed on nerve fibers of MP samples from the fundus, corpus and isthmian-cervical regions, with a successive morphometric quantification of OXT and ENK. None of the nerve fibers in the uterine fundus and corpus MPs contained ENK and the nerve fibers in the isthmian-cervical region demonstrated an ENK value of up to 94 ± 0.7 CU. A comparatively lower number of OXT-positive nerve fibers were found in the fundal MP (6.3 ± 0.8 CU). OXT-positive nerve fibers with OXT were marginally increased in corporal MP (15.0 ± 1.4 CU) and were substantially higher in the isthmian-cervical region MP (72.1 ± 5.1 CU) (p < 0.01). The distribution of OXY neurofibers showed a slight into the uterine corpus, while are highly present into the cervico-isthmic area, with influence on reproductive system and sexual disorders manifesting after surgical procedures on the cervix.