Oxygen levels in the follicle are likely to be critical to follicle development. However, a quantitative description of oxygen levels in the follicle is lacking. Mathematical modelling was used to predict the dissolved oxygen levels in the follicular fluid of the developing human follicle. The model predictions showed that follicular fluid dissolved oxygen levels are highly variable among follicles, due to the unique geometry of individual follicles. More generally, predictions showed that oxygen levels in follicular fluid increase rapidly during the initial early antral stages of follicle growth before peaking in the later early antral phase. Follicular fluid dissolved oxygen levels then decline through to the beginning of the pre-ovulatory phase, from which they increase through to ovulation. Based on the best available parameter estimates, the model predictions suggest that the mean dissolved oxygen levels in human follicular fluid during the late antral and pre-ovulatory phases range between 11 and 51 mmHg (~1.5–6.7 vol%). These predictions suggest that the human ovarian follicle is a low-oxygen environment that is often challenged by hypoxia, and are in agreement with only some published data on follicular fluid oxygen levels. Predictions are discussed in relation to follicle health and oocyte culture.