Complications such as cognitive impairment are common in stroke victims. The goal of this study was to see if there was a link between blood iron levels and post-stroke cognitive impairment (PSCI) within 2 weeks after stroke. A total of 313 patients with ischemic stroke were recruited and separated into two groups: PSCI (n = 202) and non-PSCI (n = 111). The Mini-mental state examination scale was used to evaluate the cognitive status within 2 weeks after stroke (acute phase). The serum iron levels were divided into 4 layers: Q1 ≤ 11.7 μmol/L, Q2 11.8-15.1 μmol/, Q3 15.2-19.3 μmol/L, Q4 ≥ 19.4 μmol/L, respectively. The connection between serum iron and PSCI was then investigated further using binary logistic regression, which was adjusted for confounders. The difference in serum iron levels between the PSCI and non-PSCI group was initially conducted by the Mann-Whitney test, and a significant difference was found (14.5 (11.0-17.8) vs. 16.9 (13.7-21.8), p < .001), with no confounders being adjusted. After adjusting for confounding factors, the binary regression analysis showed that the Q4 layer showed the lowest risk of PSCI, with the Q1 layer being the reference. (odds ratio (OR) = 0.297, 95% confidence interval (CI) = 0.136-0.649, p = 0.002). A decreased risk of early-onset PSCI was linked to high serum iron levels. Low serum iron levels were found to be a risk factor for acute cognitive impairment following stroke, which could help physicians identify and take intervention measures early to reduce the risk of cognitive impairment after stroke.