Mr Kerry told a Senate committee that Moscow should expect the US and EU to take measures against it on Monday should it accept and act on the expected results of this weekend's referendum regarding the future of Crimea.
Crimeans are to vote on joining Russia on Sunday in a referendum the US and EU say violates Ukraine's constitution and international law. Russia has said it will respect the results of the referendum.
Mr Kerry said: "There will be a response of some kind to the referendum itself. In addition, if there is no sign (of Russian compromise), there will be a very serious series of steps on Monday in Europe and here. My hope is they will become aware of the fact that the international community is really strongly united."
Mr Kerry will be in London today to meet Russian foreign minister Sergey Lavrov in a last-ditch bid to avert a crisis over the referendum.
He said he had spoken to Mr Lavrov already and hoped "reason would prevail".
However he stressed there is no guarantee of that.
Mr Kerry and Mr Lavrov have spoken almost daily as the Ukraine crisis has unfolded over the last month but have yet to find any common ground.