The agency also noted risk to London's dominant financial sector, "which is a major contributor to employment and public receipts".
It said Brexit will continue "to create challenging political and constitutional issues... especially if it results in a second referendum on Scottish independence or increases tensions around Northern Ireland".
The vote to leave the European Union also led to a less predictable and less stable institutional and policy framework, "highlighted by the snap election called for June", a statement said.
Prime Minister Theresa May took the country by surprise last week by calling for a general election to be held on June 8, hoping to increase her Conservative Party's slim parliamentary majority.
S&P said that although a stronger majority would give May more legitimacy and space to strike a "viable deal with the EU", there are still risks surrounding "both the election and the Brexit negotiations".