BackgroundPlasma and RBC zinc values are unrelated in hospitalized patients. The independent association of these values with important patient outcomes is unknown.ObjectivesMeasure the independent association of plasma and RBC zinc with outcomes in hospitalized patients.MethodsPlasma and RBC zinc concentrations were prospectively measured within 48 h of hospitalization in consenting patients. Data were linked deterministically with population-based health administrative data to measure each association of zinc measures with 2 outcomes (time to death from any cause and likelihood of death or urgent readmission to hospital within 30-d of discharge) after adjusting for validated outcome risk scores.ResultsIn total, 250 people admitted to medical services were studied. Patients were ill with a 1-y baseline expected death risk (IQR) of 19.9% (6.3%–37.2%). The observed 1-y and 2-y all-cause death risks were 24.5% (95% CI: 19.6%, 30.3%) and 33.2% (95% CI: 27.3%, 39.9%), respectively. Death risk increased significantly as plasma zinc concentrations decreased (P= 0.0001). This association persisted even after adjusting for the baseline expected death risk (P= 0.02) with every 2-μmol/L decrease in plasma zinc concentrations being independently associated with, on average, a 35% increase in the death risk. RBC zinc concentrations were not associated with the death risk. Neither plasma nor RBC zinc concentrations were significantly associated with the 30-d death or urgent readmission rate.ConclusionsPlasma, but not RBC, zinc concentrations are independently associated with the all-cause death risk in hospitalized medical patients. Further study is required to determine whether this association is causal and identify its potential causal pathways.Curr Dev Nutr2023;x:xx.