For a study, researchers sought to determine the relationship between 28-day mortality in patients receiving mechanical ventilation and exposure to various oxygen exposure intensities across time. The Medical Information Mart for Intensive Care IV (MIMIC-IV), which comprised patients older than 18 who required invasive mechanical breathing for at least 48 hours, provided the data that was used in this study. Participants who underwent extracorporeal membrane oxygenation (ECMO) or who began breathing more than 24 hours after being admitted to the intensive care unit were not included in the study. About 28-day mortality was the main result. The strength of correlations across time was evaluated using piece-wise exponential additive mixed models. A total of 7,784 patients in all were included in the analysis. Patients required invasive artificial breathing for an average of 8.1 days (interquartile range: 3.8–28 days), and the mortality rate at 28 days was 26.3%. Both the daily time-weighted average (TWA) arterial oxygen tension (PaO2) and a fraction of inspired oxygen (FiO2) were found to be associated with an increased 28-day mortality after controlling for baseline and time-dependent variables. The early to middle phases of the disease was when the link was highest. Daily exposure to TWA-PaO2 larger than 120 mmHg or TWA-FiO2 greater than 0.5 was found to be significantly associated with an elevated risk of mortality (hazard ratio 1.166, 95% CI 1.059-1.284). The cumulative effects of hazardous exposure (TWA-PaO2)≥120 mmHg or TWA-FiO2≥0.5 were also demonstrated. Patients on mechanical breathing should have their PaO2, and FiO2 levels routinely monitored, especially in the first and second weeks after ICU admission. There was a correlation between cumulative exposure to higher oxygen exposure intensities and an increased risk of death.