Background Age-related morbidities and frailty are associated with impaired blood pressure (BP) and heart rate (HR) recovery after standing. Here we investigate how multimorbidity affects cerebral and peripheral hemodynamics during standing in a large sample of older patients. Methods Patients were recruited from a national Falls and Syncope Unit. They underwent an active stand test (5–10 min lying +3 min standing) with monitoring of continuous BP, HR, total peripheral resistance (TPR), stroke volume (SV), and a near-infrared spectroscopy (NIRS) derived cerebral tissue saturation index (TSI). A multimorbidity count was derived from a 26-item list of conditions. Features derived from the signals included: nadir, overshoot, value at 30 s, steady-state and recovery rate. Robust linear regression was used to assess the association between multimorbidity, TSI and peripheral hemodynamics while correcting for covariates. A p-value textless0.05 was considered statistically significant. Results Multimorbidity was associated with poorer recovery of TSI at 30 s after standing (β: −0.15, CI:[−0.25–0.06], p = 0.009) independent of all peripheral hemodynamics. Impaired diastolic BP (DBP) recovery at 30s (β:−1.34, CI:[−2.29–0.40], p = 0.032), DBP steady-state (β:−1.18, CI:[−2.04–0.32], p = 0.032), TPR overshoot-to-nadir difference (β:−0.041, CI:[−0.070–0.013], p = 0.045), and SV at 30s (β:1.30, CI:[0.45 2.15], p = 0.027) were also associated with increasing multimorbidity. After sex stratification, only females demonstrated impaired TSI with multimorbidity at overshoot (β: −0.19, CI: [−0.32 -0.07], p = 0.009), 30 s (β: −0.22 [−0.35–0.10], p = 0.005) and steady-state (β: −0.20, CI:[−0.35–0.04], p = 0.023), independent of peripheral hemodynamics. Conclusions Transient cerebral oxygenation and peripheral hemodynamic responses are impaired with multimorbidity (frailty) in older patients, particularly in females. This study demonstrates the feasibility of using NIRS in this clinical context and may inform the development of clinical management strategies targeting both cerebral oxygenation and blood pressure impairments in patients with faints and falls.