Acute ischaemic stroke is associated with important mortality, morbidity, and healthcare-related costs. Age, pre-stroke functionality and stroke severity are important contributors to functional outcome. Stroke patients also risk developing infections during hospitalization. We sought to explore possible predictors of post-stroke infections and the relationship of post-stroke infection with healthcare-related costs and functional outcome. This single-centre retrospective study included 530 patients treated for ischaemic stroke between January 2017 and February 2019. Antibiotics' administration was used as a proxy for post-stroke infection. Functional outcome at 90days was assessed by the modified Rankin Scale (mRS). Total healthcare-related costs were recorded for the index hospital stay. Multivariable analysis for post-stroke infection was done with the independent factors sex, age, pre-stroke mRS, National Institutes of Health Stroke Scale (NIHSS) and diabetes mellitus. Twenty percent of patients had a post-stroke infection. NIHSS (OR 1.10, 95%CI 1.06-1.13, p < 0.0001) and diabetes mellitus (OR 2.18, 95%CI 1.28-3.71, p = 0.0042) were independent predictors for post-stroke infection. Mean total healthcare-related costs were 15,374 euro (SD 19,968; IQR 3,380-18,165), with a mean of 31,061 euro (SD 29,995; IQR 12,584-42,843) in patients with infection, compared to 11,406 euro (SD 13,987; IQR 3,083-12,726) in patients without (p < 0.0001). Median 90-days mRS was 5 (IQR 3-6) in patients with infection versus 1 (IQR 0-3.5) in patients without (p < 0.0001). In patients, admitted for acute ischaemic stroke, stroke severity and diabetes mellitus were identified as the main predictors for post-stroke infection. Hospital-acquired infections were associated with increased costs and worse functional outcome.