Background: The timing and dose of exclusive nutrition support (ENS) have not been investigated in previous studies aimed at validating the modified Nutrition Risk in Critically Ill (mNUTRIC) score. We therefore evaluated the mNUTRIC score by determining the association between dose of nutrition support and 28-day mortality in high-risk patients who received short- and longer-term ENS (≤ 6 days vs. ≥ 7 days). Methods: A prospective cohort study included data from 252 adult patients with > 48 h of mechanical ventilation in a tertiary care institution in Singapore. The dose of nutrition support (amount received ÷ goal: expressed in percentage) was calculated for a maximum of 14 days. Associations between the dose of energy (and protein) intake and 28-day mortality were evaluated with multivariable Cox regressions. Since patients have different durations of ENS, only the first 6 days of ENS in patients with short- and longer-term ENS were assessed in the Cox regressions to ensure a valid comparison of the associations between energy (and protein) intake and 28-day mortality. Results: In high-risk patients with short-term ENS (n = 106), each 10% increase in goal energy intake was associated with an increased hazard of 28-day mortality [adj-HR 1.37 (95% CI 1.17, 1.61)], and this was also observed for protein intake [adj-HR 1.31 (95% CI 1.10, 1.56)]. In contrast, each 10% increase in goal protein intake in high-risk patients with longer-term ENS (n = 146) was associated with a lower hazard of 28-day mortality [adj-HR 0.78 (95% CI 0.66, 0.93)]. The mean mNUTRIC scores in these two groups of patients were similar. Conclusion: When timing and dose of nutrition support were examined, the mNUTRIC did not differentiate high-risk patients who would derive the most benefit from nutrition support.