Introduction Knowledge of fetal physiology during labor has been largely generated from animal models. Our team recently developed a new index to assess parasympathetic activity using different experimental protocols to obtain acidosis. The objective of the present study was to discuss the different protocols and to review other models proposed in the literature. Material and methods Pregnant ewes underwent a surgical procedure at the 123 ± 2 days gestational age (term = 145 days). Three experimental protocols were used: protocol A consisted of 25%, 50% and 75% umbilical cord occlusion (UCO) for 20 min. Protocol B consisted of partial 75% UCO until reaching a pH < 7.10. Protocol C consisted of brief, repetitive complete occlusion until severe acidosis occurred. Hemodynamic and blood gas parameters were compared to those of the stability period before UCO. Results Protocol A led to a progressive response depending on the degree of occlusion (decrease in fetal heart rate, arterial hypertension and pH). Protocol B led to severe acidosis, although the duration of UCO varied per animal. Protocol C also progressively led to acidosis. We observed high inter individual variability in the acidosis response. Conclusion Pregnant ewes are a relevant model for exploring fetal response to acidosis. The frequency of UCO and partial or complete occlusion should be adapted to the expected effects. Knowledge of these protocols is important to respect ethical guidelines and to reduce the required number of animals. Moreover, it is important to consider the high individual variability of the acidosis response in the interpretation of the results.