Background: Intra-cytoplasmic sperm injection (ICSI) is used in assisted reproductive technology (ART) laboratories. However, there is no consensus regarding the precise time intervals within ICSI cycles [oocyte pick up (OPU), oocyte denudation (DN), and ICSI], and results are inconsistent and contradictory. Thus, we aim to evaluate whether there is a concordance regarding the time intervals used in different laboratories and a concrete time that gives better laboratory and reproductive results. Methods: A systematic review of the literature until December 31, 2020, was performed with the keywords “Oocyte Denudation/Denudation/Oocyte,” “Intra-cytoplasmic Sperm Injection/ICSI,” “Oocyte/Oocyte maturation/ cumulus,” and “Cumulus removal/ removal.” Articles and abstracts in English and involving human subjects referring to the effects of oocyte DN time on embryo development and clinical outcomes were included. Results: Of the 250 evaluated articles, 20 (including 15 full articles and 5 abstracts) were included in this review. Fifteen studies analysed the effect of OPU-DN time on embryo development and clinical outcomes. Most of these studies concluded that OPU-DN time did not influence ICSI outcomes, but some suggested that oocytes should be incubated for a short time before DN to improve oocyte maturity and enhance ICSI outcomes. In addition to reports on positive or negligible effects, adverse effects were reported in 8 studies on DN-ICSI timing. Neither OPU-DN nor DN-ICSI time could improve live birth rate. Conclusions: Oocytes should be pre-incubated for a short duration (preferably < 4 h) before DN according to the ART laboratory schedule. More randomised controlled trials are warranted to clarify the effect of DN-ICSI timing on ICSI outcomes.