New-onset altered level of consciousness (ALC) is challenging in emergency rooms (ERs), requiring focused attention. The COVID-19 pandemic has impacted healthcare systems globally, influencing ER dynamics. This study compared ALC before (BC) and after (AC) the coronavirus disease 2019 outbreak, focusing on etiology, disposition, and outcomes. This was a retrospective, multicenter study of four university hospitals in charge of an area of about five million people in South Korea. All cases were reviewed within a consortium of board-certified faculties and compared between BC (February 2018 to January 2020) and AC (March 2021 to February 2023. We reviewed to find 17,913 patients who visited the ER due to ALC, of whom 7,988 and 9,925 were in BC and AC, respectively. The overall incidence of ALC in the ER was 3.1%, higher in AC (BC vs. AC, 2.5% vs. 3.7%, p < 0.001). The most common etiology was Metabolic cause (24.8%), followed by Systemic infection (18.0%). Intracranial etiologies accounted for 29.7% of the total. Hospitalization rate increased from BC to AC (54.5–59.3%, p < 0.001). The overall mortality was 16.2%, and 5.3% of the patients with ALC died in the ER. ALCs dut to cardiogenic and vascular etiology had the highest mortality (26.8%). This study marks the first investigation on ALC in the ER comparing BC and AC.