Tim Oliver of the London School of Economics, a specialist in British foreign policy, said Brexit would cause the US an "unwanted headache".
"The UK has a special relationship with the USA but that is most true in the three areas of nuclear weapons, intelligence and special forces," he told AFP.
"The wider relationship fits into a much wider and special US-European relationship."
Oliver argued that a Brexit would also cause problems for Beijing, adding: "Few in the UK appreciate that one of the longest-standing supporters of European integration has been China."
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