Introduction: It is recognized that Methemoglobin (MetHb) levels are elevated in sepsis due to increased nitric oxide production. The degree of MetHb elevation may have prognostic significance, and unrecognized elevation may reflect outcome in non-septic acute hospital admissions. The additive outcome effect of MetHb, ionized calcium (iCa), and lactate may be of prognostic value. Methods: In a retrospective observational study. co-oximeter data from 1000 admissions over 18 months to a general ICU was interrogated for arterial MetHb, lactate, and iCa levels. Patient demographics, admission and ultimate diagnoses allowed classification into categories of Septic / Non-Septic, Survivor (S) / Non-Survivor (NS). T-testing after logistic transformation or Mann Whiney U testing was used to compare MetHb (%), lactate (mmol/L), iCa (mmol/L) levels between septic (n= 273) and non-septic (n=650) cases, also S (n=809) and NS (n=115). A regression analysis was also performed to determine the contribution of the above factors to outcome. p<0.05 was accepted for statistical significance. Results are expressed as median (Md) and range (R) or mean (Me) and 95% CI. The fit of the model was assessed with ROC analysis and the Hosmer Lemeshow (HL) test. Results: There was no age difference between the septic and non-septic groups. Of 1000 admissions, 927 had MetHb data. 2 patients had MetHb >2 (Md 1.0, range 0.5–3.1). Those with a diagnosis of sepsis (n=273) had significantly higher MetHb levels than non-septic patients (Md 1.0, R 0.5 – 3.1 vs 1.0, 0.5 – 2.0). NS with sepsis (n=46) had significantly higher MetHb levels than NS without sepsis (n=69) (Md 1.0, R 0.5 – 1.7 vs 0.9, 0.5 – 1.6). iCa was lower in NS than S (Md 1.04, R 0.45 – 1.9 vs 1.09, 0.35 – 1.76), and also lower in septic than non-septic patients, but with no difference between S and NS with sepsis. Lactate was significantly higher in NS than S (Me 2.7, 95% CI 2.3 – 3.2 vs 1.37, 1.3 – 1.4). Lactate was also significantly higher in septic compared to non-septic patients (1.6, 1.5 – 1.8 vs 1.4, 1.36 – 1.5) Age, presence or absence of sepsis, and lactate were included in the logistic regression analysis for outcome, with AUC for the ROC of 0.77 and HL>0.3. Conclusions: Methemoglobin levels above 2% are rare. MetHb is significantly elevated in our patient population with sepsis however the degree of elevation at admission in our group was not predictive of outcome. iCa, while lower in NS, does not predict outcome in a population with sepsis. Lactate elevation at admission, in this group, correlates with outcome, and the combination of lactate, age and sepsis shows comparable predictive value to established formulae.