Musculoskeletal strain or sprain: This is often the most common cause of pain in one lower extremity, resulting from overuse, injury, or trauma to the muscles, tendons, or ligaments.

Peripheral neuropathy: Conditions such as diabetic neuropathy or nerve entrapment (e.g., sciatica) can cause pain in one lower extremity due to nerve damage or compression.
Osteoarthritis: Wear and tear on the joints, particularly in the hips, knees, or ankles, can lead to pain in one lower extremity, especially with weight-bearing activities.
Deep vein thrombosis (DVT): Although less common, DVT can cause pain, swelling, and warmth in one lower extremity due to a blood clot in the deep veins.
Cellulitis or skin infection: Bacterial infections of the skin can cause pain, redness, and swelling in one lower extremity.

Acute arterial occlusion: A sudden blockage of an artery in the lower extremity can cause severe pain, pallor, pulselessness, poikilothermia, paresthesias, and paralysis, requiring immediate medical attention.
Compartment syndrome: Increased pressure within a muscle compartment can cause severe pain, especially with passive stretching, and can lead to permanent damage if not promptly treated.
Osteomyelitis or septic arthritis: Infections of the bone or joint can cause severe pain, fever, and swelling, and require urgent antibiotic treatment.
Ectopic fracture: A fracture in a bone weakened by a pathological process (e.g., metastatic cancer) can cause sudden, severe pain.

Complex regional pain syndrome (CRPS): A chronic pain condition characterized by severe, burning pain, usually following an injury or trauma.
Erythromelalgia: A rare disorder that causes burning pain, heat, and redness in the hands and feet, often related to myeloproliferative disorders.
Peripheral artery aneurysm: A bulge in an artery in the lower extremity can cause pain, swelling, and potentially lead to rupture.
Neoplastic processes: Tumors, either primary or metastatic, can cause pain in one lower extremity, although this is less common.