Background <p>Sirtuins and FoxO1 are reported to be important in the pathophysiology of preeclampsia. This study aimed to investigate whether serum FoxO1 and SIRT2 concentrations differ between preeclampsia and normal pregnancy and also to compare these markers in early- and late-onset preeclampsia.</p> Methods <p>This cross-sectional study was conducted on 27 women with early-onset preeclampsia, 27 women with late-onset preeclampsia, and 26 healthy normotensive pregnant controls. Maternal serum levels of FoxO1 and SIRT2 were measured with the use of an enzyme-linked immunosorbent assay kit.</p> Results <p>The mean maternal serum FoxO1 levels were significantly lower both in early-onset (9.1 ± 3.8 vs. 29.1 ± 3.2, <i>p</i> &lt; 0.001) and late-onset preeclampsia (2.6 ± 1.6 vs. 29.1 ± 3.2, <i>p</i> &lt; 0.001) than the normotensive pregnancies. The mean maternal serum FoxO1 level of late-onset preeclampsia was significantly lower than the early-onset preeclampsia group (2.6 ± 1.6 vs. 9.1 ± 3.8, <i>p</i> &lt; 0.001). The mean maternal serum SIRT2 levels were significantly lower both in early-onset (4.5 ± 2.1 vs. 6.3 ± 0.9, <i>p</i> &lt; 0.001) and late-onset preeclampsia (2.1 ± 0.6 vs. 6.3 ± 0.9, <i>p</i> &lt; 0.001) than the healthy pregnancies.</p> Conclusions <p>FoxO1 and SIRT2 may be biomarkers for early detection of preeclampsia and potential therapeutic targets in the pathophysiology of preeclampsia<b>.</b></p>