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Sex estimation is a necessary part of forensic and osteological analyses of skeletal human remains in the construction of a biological profile. Several skeletal traits are sexually dimorphic and used for skeletal sex estimation. The human mandible and morphological traits therein have been long used for sex estimation, but the validity of using the mandible in this purpose has become a concern. In this study, we examined the potential of artificial intelligence (AI) and especially deep learning (DL) to provide accurate sex estimations from the mandible. We used 193 modern South African mandibles from the Human Osteological Research Collection (HORC) in the Sefako Makgatho Health Sciences university with known sex to conduct our study. All mandibles were photographed from the same angle and the photographs were analyzed with an open-source DL software. The best-performing DL algorithm estimated the sex of males with 100% accuracy and females with 76.9% accuracy. However, further studies with a higher number of specimens could provide more reliable validity for using AI when building the biological profile from skeletal remains., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)