Heart failure (HF) induces skeletal muscle alterations that impair physical function and quality of life. However, most studies have been performed in HF with a reduced ejection fraction (HFrEF) whereas skeletal muscle remodelling in HF with preserved ejection fraction (HFpEF) remains poorly explored. The present study, therefore, used an obese cardio-metabolic model to investigate functional, morphological, and vascular alterations that occur in the skeletal muscles of HFpEF rats. Methods: Lean (n=8) and obese (n=8) diabetic Zucker fatty/spontaneously hypertensive heart failure F1 hybrid (ZSF1) rats were compared at 20 weeks of age and cardio-metabolic function assessed (i.e. body weight, blood glucose levels and mean arterial pressure). Tibialis anterior (TA) fibre size (stained with haematoxylin and eosin) was evaluated alongside contractility measures for in vitro soleus function (specific force, shortening velocity and power) and in situ extensor digitorum longus (EDL) function (force and fatigability) following stimulation across a range of frequencies. Anaesthesia was induced with 4% isoflurane in 100% oxygen and maintained throughout experiments by constant jugular infusion (30-35mg kg-1 hr-1) of alfaxalone (Jurox, Crawley, UK). Femoral artery blood flow at rest and during stimulation was quantified using Transonic (0.7PSB; Ithaca, NY, USA) perivascular flowprobes. Data were compared by unpaired Student t test and are presented as mean±SEM. Results: HFpEF rats were obese (424.50±11 vs. 549.50±11 g body weight; P<0.05), hyperglycaemic (8.50±0.80 vs. 16.80±0.50 mmol.L-1; P<0.05) and hypertensive (151.34±3.14 vs. 177.44±4.39 mmHg; P<0.05) compared to lean controls. HFpEF rats developed ~40% fibre atrophy in the TA (3172±527 vs. 5667±332 µm2; P<0.05). Despite no differences (P>0.05) in soleus specific forces or shortening velocities, maximal power was lower in HFpEF compared to controls by ~30% (0.95±0.04 vs. 1.33±0.11 W cm-2; P<0.05). Compared to controls, both EDL twitch and maximal tetanic absolute forces were impaired in HFpEF by ~30% (57±5 vs. 42±4 g and 225±27 vs. 151±16 g, respectively; P<0.05), yet hindlimb blood flow was higher at rest (1.75±0.20 vs. 2.84±0.47 ml min-1; P<0.05) but lower during contractions (5.44±0.70 vs. 3.74±47 ml min-1; P<0.05). Conclusions: HFpEF induced skeletal muscle weakness, fibre atrophy and contractile dysfunction alongside impaired blood flow response during contractions. While the mechanisms underlying these deficits remain unclear, these data suggest that vascular, functional, and structural impairments of skeletal muscle contribute to life-limiting symptoms observed in patients with HFpEF.