Oxygen-induced oxidative stress (OS) has damaging effects in the perinatal period. For now there is a lake of evidence that OS occurs in babies with retinopathy of prematurity (ROP) We tests the hypothesis that a strict oxygen policy may minimize postnatal OS reducing severity of ROP. Multicenter prospective cohort study (72 newborns), using a common clinical management protocol with a strict control of oxygen administration. Assessment of biochemical markers of OS in blood samples at birth and on days 7, 14, and 21. Sixteen babies (22.2 per cent) developed ROP stage 1-2. No severe form of ROP was observed. Birth weight and O2 administration in delivery room were the factors significantly associated with the development of ROP stage 1-2. Prematurity and O2 administration in delivery room are the main factors coming into play in the course of ROP. Because room air is richer in oxygen than intrauterine environment, higher OS can be minimized, as well as incidence and severity of ROP, using standardized management with a restricted oxygen breathing policy.