Although low serum bicarbonate level is known to be associated with adverse outcomes in patients with chronic kidney injury, it is unclear whether low serum bicarbonate level is associated with the development of acute kidney injury (AKI). The purpose of our study was to determine whether serum bicarbonate levels at admission could be a risk factor for AKI development and mortality in hospitalised patients. We retrospectively enrolled 17,320 adult patients who were admitted to the academic teaching hospital from January 2013 to December 2013. Patients were divided into 2 groups based on the first measurement of serum bicarbonate level at admission. The incidence of AKI was higher in patients with low serum bicarbonate level than in those with normal serum bicarbonate level (8.0% vs. 4.1%). Low serum bicarbonate levels at admission were significantly associated with the development of AKI. In addition, low serum bicarbonate levels also independently predicted the 90-day mortality. Pre-existing low bicarbonate levels and subsequent development of AKI increased in-hospital mortality by 15 times compared with that in patients with normal bicarbonate levels and no AKI. Low serum bicarbonate levels may be associated with the development of AKI and high mortality in hospitalised patients.