Stock index futures were lower for the fourth straight day as investors braced for the Federal Reserve's policy meeting and a referendum on Britain's European Union membership.
The Federal Open Market Committee (FOMC) will commence its two-day meeting on Tuesday to decide whether the U.S. economy has recovered enough to be able to absorb an interest rate hike.
While traders have discounted a hike this month, they will parse Fed Chair Janet Yellen's speech at a conference on Wednesday for clues on the health of the economy and the timing of the next hike.
Yellen, who had been dropping hints last month of a rate hike in the near term, toned down her comments after a dismal May employment report set off fresh concerns of the strength of the economy.
Traders have priced in a 17.9 percent chance of a rate hike next month and a 29 percent chance in September, according to CME Group's FedWatch tool.
Oil prices extended losses as investors remained nervous over the rising possibility of Britain exiting the European Union when it votes on June 23.
Recent opinion polls have indicated growing support for Brexit, adding to investor concerns.
Reduced appetite for risky assets across the globe sent the yield on the 10-year German bond below zero for the first time ever.
Investors will also keep an eye on U.S. retail sales data, which is expected to have risen 0.3 percent in May from a 1.3 percent rise the previous month. The data is expected at 8:30 a.m.
Wall Street closed lower for the third straight session on Monday, dragged down by tech giants Microsoft and Apple.
Chinese search engine company Baidu fell 6 percent to $153.74 premarket after lowering its current-quarter revenue forecast.
Valeant rose 4.7 percent after CEO Joseph Papa purchased 202,000 shares.
Twitter rose 2.7 percent to $14.95 after Goldman Sachs added the micro-blogging site to its list of companies that could be bought in the next year.