Background The aim of this study is to evaluate whether lower serum levels of insulin‐like growth factor 1 (IGF‐1) in the acute phase of ischemic stroke are associated with higher risk of post‐stroke depression (PSD) over a 1‐year period. Methods The subjects were first‐ever acute ischemic stroke (AIS) patients who were hospitalized from July 1, 2014 to August 31, 2015. The study also included 120 age‐matched and sex‐matched healthy controls from the same geographical area. Fasting blood samples were collected within 24 hours of admission for IGF‐I measurement. Neurological and neuropsychological evaluations were conducted at a 1‐year follow‐up. Results Two‐hundred twenty‐five patients were observed for a 1‐year follow‐up, and 74 of these patients (32.9%, 95%CI: 26.8%‐39.0%) were diagnosed with PSD. The depression distribution across the IGF‐1 quartiles ranged between 61.4% (first quartile) and 8.9% (fourth quartile). In a multivariate model using the first quartiles of the IGF‐1 versus quartiles 2 through 4, together with the significant clinical variables, the marker displayed prognostic information, and the odds ratio (OR) for first quartile was 3.35 [95% CI, 1.88‐6.79; P = 0.001]. Conclusion The data showed that low serum IGF‐1 levels at admission are associated with a high risk of developing PSD, suggesting that these alterations might be involved in the pathophysiology of depression symptoms in stroke patients.