Aim Severe early-onset (SEO) pre-eclampsia (PE) is a leading cause of maternal and fetal morbidity in the UK and at present there is not a reliable clinical tool to predict the disease’s onset. Hypertension (essential in the diagnosis of PE) has been associated with dysregulation of numerous plasma proteins, both in pregnant and non-pregnant studies. The aim of this work is to identify whether the angiotensinogen to kallikrein ratio is altered in the first trimester of pregnancies that go on to develop pre-eclampsia. Method We analysed first trimester plasma samples obtained from a phenotypically matched cohort of women who went on to develop SEOPE (n = 30) and compared them to those who did not (n = 30) with angiotensinogen and kallikrein concentrations obtained through label-free mass spectrometry (HPLC-MSE). Results There was no significant difference between the demographics of the two groups. All women in the PE group had abnormal Uterine artery waveform Doppler at 24 weeks, whereas the “normal” group did not. Angiotensinogen was up-regulated (p < 0.001) and Kallikrein was down-regulated (p < 0.002) in first trimester PE samples with a correlation (r) of –0.55 (–0.71 to –0.34). Conclusion Angiotensinogen: Kallikrein is significantly altered in women who develop severe early-onset pre-eclampsia and may play a role in a future clinical for the condition.