Geopolitical worries were expected to continue driving near-term direction, including concern over the impact of the earthquake and nuclear crisis in Japan, and unrest in the Middle East and North Africa.
Further disruptions to supply chains were seen hitting individual companies in the wake of Japan's massive earthquake, with Sony (SNE.N) cutting output at five more plants and Toyota Motor (TM.N) saying it would keep assembly lines shut until at least Saturday.
Ford Motor (F.N), however, said on Wednesday it had felt no immediate impact or disruption from the earthquake.
Japan estimated direct damage from the earthquake and tsunami to be 16-25 trillion yen ($185-$308 billion), making it the world's costliest natural disaster.
Concerns over the euro zone debt crisis will again be in focus as Portugal's parliament was expected to reject government austerity measures in a vote scheduled for 1500 GMT, with Prime Minister Jose Socrates threatening to resign if the opposition rejected the proposals.
Violence in parts of the oil-rich Middle East and North Africa region, including Libya, Syria and Yemen lifted Brent crude futures to around $116 a barrel, reigniting concerns of inflationary pressure on fragile economic recovery.
Shares on Wall Street closed lower on Tuesday, snapping a three-day winning streak.
In company news, General Motors (GM.N) sold its preferred shares in auto lender Ally Financial Inc for $1 billion to strengthen its balance sheet.
In Europe, the FTSEurofirst 300 .FTEU3 index of top shares fell 0.2 percent in early trade.
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