Intradialytic hypotension (IDH) and peridialytic blood pressure (BP) trends are associated with morbidity and mortality in haemodialysis (HD) patients. We aimed to characterise the respective influence of volume status and small solutes variation on peridialytic systolic BP (SBP) trends during HD. We retrospectively analysed the relative peridialytic SBP decrease in 647 prevalent outpatients attending for their mid-week session with corresponding pre- and post-HD bioelectrical impedance analysis. Mean SBP decreased by 10.5 ± 23.6 mmHg. Factors positively associated with the relative decrease in SBP were: serum sodium (Na) decrease, body mass index, serum albumin, dialysis vintage, ultrafiltration rate and urea Kt/V (p < 0.05 for all). Antihypertensive medications and higher dialysate calcium were negatively associated with the relative decrease in SBP (p < 0.05 for both). Age had a quadratic relationship with SBP trends (p < 0.05). Pre-HD volume status measured by extracellular to total body water ratio was not associated with SBP variation (p = 0.216). Peridialytic SBP trends represent a continuum with serum Na variation being a major determinant while volume status has negligible influence. Middle-aged and overweight patients are particularly prone to SBP decline. Tailoring Na and calcium dialysate concentrations could influence haemodynamic stability during HD and improve patient experience and outcomes.