BACKGROUND: Knee osteoarthritis (OA) is associated with changes in corticospinal and intracortical excitability which may be due to persistent pain. OBJECTIVE: To investigate the cortical excitability profile of the femoral quadriceps in people with knee OA and healthy volunteers. METHODS: Cortical excitability was assessed using transcranial magnetic stimulation (TMS) in 7 participants with knee OA and 6 age- and sex-matched healthy volunteers. The motor evoked potential (MEP), cortical silent period (CSP), short intracortical inhibition (SICI) and intracortical facilitation (ICF) of the rectus femoris (RF), vastus medialis (VM) and vastus lateralis (VL) were measured using standard single pulse and paired-pulse TMS techniques. Data analysis was performed using Mann-Whitney test considering alpha <0.05. RESULTS: Participants with knee OA demonstrated reduced MEP amplitude in the RF and VM muscles and augmented MEP amplitude in the VL muscle. SICI was reduced only in the RF and ICF was reduced in the VM and VL. CSP was reduced in all muscles. CONCLUSION: People with knee OA exhibit altered corticospinal and intracortical excitability profile in specific portions of the quadriceps muscle. This suggests a possible adaptive strategy to maintain quadriceps motor activity.