Hyperbilirubinemia is a higher-than-normal level of bilirubin in the blood. Hyperbilirubinemia may refer to increased levels of conjugated, unconjugated or both conjugated and unconjugated bilirubin. The causes of hyperbilirubinemia can also be classified into prehepatic, intrahepatic, and posthepatic.  
Prehepatic causes are associated mostly with an increase of unconjugated (indirect) bilirubin. They include:
* Hemolysis or increased breakdown of red blood cells (for example hematoma resorption)
Intrahepatic causes can be associated with elevated levels of conjugated bilirubin, unconjugated bilirubin or both. They include:
* Neonatal hyperbilirubinemia, where the newborn's liver is not able to properly process the bilirubin causing jaundice
* Hepatocellular disease
** Viral infections (hepatitis A, B, and C)
** Chronic alcohol use
** Autoimmune disorders
* Genetic syndromes:
** Gilbert's syndrome – a genetic disorder of bilirubin metabolism that can result in mild jaundice, found in about 5% of the population
** Rotor syndrome: non-itching jaundice, with rise of bilirubin in the patient's serum, mainly of the conjugated type
** Dubin–Johnson syndrome
** Crigler–Najjar syndrome
* Pharmaceutical drugs (especially antipsychotic, some sex hormones, and a wide range of other drugs)
** Sulfonamides are contraindicated in infants less than 2 months old (exception when used with pyrimethamine in treating toxoplasmosis) as they increase unconjugated bilirubin leading to kernicterus.
** Drugs such as protease inhibitors like Indinavir can also cause disorders of bilirubin metabolism by competitively inhibiting the UGT1A1 enzyme.
Post-hepatic causes are associated with elevated levels of conjugated bilirubin.  These include:
* Unusually large bile duct obstruction, e.g. gallstone in common bile duct (which is the most common post-hepatic cause)
* Biliary stricture (benign or malignant)
* Cholangitis
* Severe liver failure with cirrhosis (e.g. primary biliary cirrhosis)
* Pancreatitis
Cirrhosis may cause normal, moderately high or high levels of bilirubin, depending on exact features of the cirrhosis.
To further elucidate the causes of jaundice or increased bilirubin, it is usually simpler to look at other liver function tests (especially the enzymes alanine transaminase, aspartate transaminase, gamma-glutamyl transpeptidase, alkaline phosphatase), blood film examination (hemolysis, etc.) or evidence of infective hepatitis (e.g., hepatitis A, B, C, delta, E, etc.).