In the neonatal intensive care unit (NICU), maintaining an oxygenation level that avoids both hypoxemia and hyperoxemia is challenging. Pulse oximetry has become fundamental for noninvasive monitoring of saturation of peripheral oxygen (Sposub2) in preterm newborns. Purpose: The aim of this systematic review is to determine Sposub2 target values in order to avoid hypoxemia or hyperoxemia and complications arising from these. Method and Search Strategy: For this systematic review, articles were audited from 2010 to 2020 using the PRISMA guidelines. PubMed, MEDLINE, Google Scholar, and Scopus databases were used, and search terms were related to use of pulse oximetry in the NICU. Results: The result showed that 12 of 20 (60%) studies focused on target values but without a unanimous agreement on values, although 5 of 12 studies (41.66%) suggested a lower value target of 85% and 4 of 12 studies (33.33%) recommended 95% as the higher target value. Other authors showed no difference in the incidence of adverse events comparing different target values and focused the importance more on the fluctuation of the value than on the target value itself. Implication for Practice: Reaching a balance in the oxygen administration so as to avoid potential complications associated with hypoxemia or hyperoxemia is a challenge for the clinicians. Implication for Research: Further studies on fluctuation of Sposub2 comparing different starting targets could better clarify the role of fluctuations and the absolute target values. Video abstract available at https://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx.