<p>The aim of the study was to evaluate the time course of changes of serum MMP-2 and MMP-9 levels in patients in the acute period after ischemic stroke during clinical and functional recovery. The group consisted of 114 patients with cerebral ischemic stroke. There were three groups of patients: Group 1, mild stroke (<i>n</i> = 57 patients); Group 2, moderate stroke (<i>n</i> = 25 patients); Group 3, severe stroke (<i>n</i> = 32 patients). The observation continued for 14 days. Assessments were performed at two time points: I–within the first 48-72 hours of disease onset, and II–on day 14. NIHSS scale was used for estimation. MMP-2 and MMP-9 were measured in the blood serum using ELISA. Statistical analysis of the results was performed using the Statistica 13.0 software. In the patients of groups 1 and 2, there was a statistically significant decrease in the score according to the NIHSS and mRs scales (<i>p</i> &lt; 0.001) during the observation period while in the patients of group 3, there were no significant changes (<i>p</i> = 0.157 and <i>p</i> = 0.315, respectively). MMP-2 and MMP-9 did not significantly differ between the control group and groups of patients in two points of observation. A significant decrease in the MMP-2 level was revealed in the group 3 patients compared to the group 1 (<i>р</i>_1–3 = 0.03 and <i>р</i>_1–3 = 0.014, respectively). The level of MMP-2 decreased during the acute period in the group 3 (<i>р</i>_I–II = 0.043). A negative correlation between mRs_I and MMP-2_II (<i>r</i> = –0.611, <i>p</i> = 0.027) was revealed in the group 2. Between-group analysis did not reveal any changes in the MMP-9 level to the end of the period of observation. In the group 1, ΔMMP-9 = 75[–38; 302] ng/mL positively correlated with mRs_II (<i>r</i> = –0.613, <i>p</i> = 0.034). MMP-2 and MMP-9 in the blood serum of patients are promising prognosis biomarkers of ischemic stroke but their time-related variability and multifunctionality limit their clinical application.</p>