A luteal phase defect (LPD) is a clinical problem leading to infertility and is characterized by reduced progesterone levels during the luteal phase. Serum lipoperoxidation is an expression of cellular hypoxic damage occurring under all stress-oxidative conditions. Forty-eight consecutive infertility patients, according to the infertility class II of the WHO classification, underwent clinical observation. Twenty-five patients ovulated constantly with a normal luteal phase, while the other 23 had a LPD, hormonally and histologically assessed. The luteal phase was monitored biochemically by titration of progesterone, oestradiol, and serum lipid peroxides during the ovulatory period and 6–12 days after ovulation. The mean plasmatic concentration of oestradiol was not statistically different between the LPD and the normal-cycle groups, while a statistically significant difference was found for progesterone plasmatic concentrations between the LPD and the normal-cycle groups (p < 0.05); a greater statistical difference was also found in the mean serum lipoperoxide titration (p < 0.001). These findings suggest that serum lipoperoxidation titration may be a useful tool in the study of the interactions between hormonal milieu and sympathetic activity.