Gonad histopathology data are increasingly being used as indicators of reproductive disorders since they provide a definite biological end-point of historical exposure to endocrine disruptors. Here, a comparative study of some reproduction biological aspects, such as gonad histology, gonadosomatic index (GSI), hepatosomatic index (HSI) and condition index (CI) of mature Grass Goby (Zosterisessor ophiocephalus), was carried out in Bizerta lagoon where chemical contamination is proven and in a reference station free of this type of contamination. For this purpose, female and male gobies were collected during the breeding season (April 2006) in three stations in Bizerta lagoon (Menzel-Abderrahemen, Menzel-Bourguiba and Menzel-Jemil), differently impacted by contaminants, including PAHs, PCBs, DDT, organotins and heavy metals, and in the seaward entrance of Ghar el Melh lagoon (reference station). In both sexes, we detected the presence of an overall weaker GSI in Bizerta lagoon than in control fish. These GSI alterations were accompanied by most pathological changes. In females, a higher incidence of oocyte lesions (atretic oocytes and cytoplasmic retraction) was found in stations located near agricultural activity zones. Histologic observation of the testes revealed, as well, abnormalities in Bizerta lagoon fish such as germ cells syncytia, vacuolated germ cells and increase of gaps in the interstitium between lobules. These abnormalities were detected with a high prevalence in stations influenced by industrial and/or urban activities. This study provides insights on the effects of various environmental stressors on Z. ophiocephalus reproductive health. Nevertheless, much research is needed to understand the cause of observed changes and their long-term effect on fish reproductive health, on population fitness and on this species survival in Bizerta lagoon.