Objective: To investigate whether the serum levels of metastin and PIGF and chitotriosidase activity early in pregnancy differ in women who develop pre-eclampsia from those who remain normotensive. Study design: A retrospective case-control study of prospectively collected data. Thirty healthy pregnant women and 31 women with pre-eclampsia were included in the study. Serum samples were collected at 11-14 weeks and stored at -70 °C. Levels of metastin, PIGF and chitotriosidase activity were measured in serum from pregnant women with subsequent development of pre-eclampsia and matched controls. Results: Mean maternal serum metastin (1554 ± 385 pmol/L vs 1995 ± 375 pmol/L, p < 0.001) and PIGF (111.9 ± 7.0 pg/mL vs 124.9 ± 13.5 pg/mL, p < 0.001) levels were significantly lower and chitotriosidase activity was significantly higher (681.6 ± 248.3 nmol/mL/h vs 527.7 ± 223.1 nmol/mL/h, p < 0.01) in women who subsequently developed pre-eclampsia than in those who remained normotensive. The areas under the curve equal to 0.797, 0.831 and 0.681 (p < 0.001, p < 0.001 and p < 0.01) for metastin, PIGF, and chitotriosidase respectively were determined for the prediction of pre-eclampsia. Conclusions: Metastin and PIGF levels and chitotriosidase activity are altered in the first trimester serum of women destined to become pre-eclamptic, reflecting placental dysfunction. Metastin, like PIGF, may have a potential to be used as a first-trimester biomarker of pre-eclampsia. © 2012 Elsevier Ireland Ltd. All rights reserved.