Mr Denham called on ministers to "do what they could" to stop Ford pulling out of the city, if that was their plan.
He said: "It would be a huge blow it is the last place in the UK where Ford still make complete vehicles. In many ways it would mean the end of Ford's involvement in the UK.
"I don't think that the government should simply say that it is unfortunate.
"It might be fords strategy maybe to shift all of its production to other EU and non EU countries and I think that the Government needs to put very strong pressure on Ford to rethink their decision, if closing the Southampton plant is the decision they have made."