The Brexit vote stunned markets in June, and Donald Trump shocked investors in November. The Italians may be next.

On Dec. 4, Italian citizens will vote in a referendum on whether to overhaul their national constitution, which probably has to be amended if Prime Minister Matteo Renzi is going to push badly needed economic reforms through the country's complicated lawmaking process.

The vote is widely seen as determining Renzi's political fate, and he may resign if a "no" vote prevails. Opinion polls show most Italians opposing the proposed constitutional changes, which economists say Italy desperately needs if it's going to streamline its government and spark growth.

HSBC warned in a note to clients after the U.S. election that a global surge in anti-establishment feeling — exemplified by the U.K. referendum and the U.S. presidential election — could embolden populist views already widespread in Italy.

The elevated political risk in the country is starting to get priced into stocks and bonds.

Italian stocks have been on the decline in 2016 as the country grapples with slowing growth, high unemployment and distress in its banking system. So far this year the Italian benchmark, FTSE MIB, is down roughly 23 percent, compared with the STOXX Europe 600 index which has fallen about 7 percent. The FTSE MIB is currently trading at an eight-week low as investor concern around the outcome of the referendum grows.

The losses are most visible in Italian banks with UniCredit, Unione di Banche Italiane, Banca Poplare di Milano and Banca Monte dei Paschi di Siena all down more than a whopping 60 percent so far this year.

Italian banks have been under pressure because of a high number of nonperforming loans they're holding, and their worries about whether they can recapitalize. According to the International Monetary Fund, Italian banks hold roughly $400 billion in troubled loans. Currently, the six worst-performing stocks in the European banking index are all Italian.

And the situation could become even worse for those debt-ridden banks if the "no" vote wins. It could undermine the stability of the European financial system and make it more difficult for the Italian banks to turn the corner. "Raising capital will be more difficult with a big 'no,'" said Alberto Gallo, head of global macro strategies at asset management firm Algebris Investments.

"Political stability might hurt the Italian finance system — specifically the banks which are trying to clean up their balance sheet," Andrea Montanino, director at the Atlantic Council and a former executive director of the IMF, told CNBC.
Marchers in Naples, Italy, hold placards and chant slogans as they protest Italian Prime Minister Matteo Renzi before a reform referendum to be held Dec. 4.
Stringer | Anadolu Agency | Getty Images
Marchers in Naples, Italy, hold placards and chant slogans as they protest Italian Prime Minister Matteo Renzi before a reform referendum to be held Dec. 4.

"People may not have been looking seriously at this pre-Brexit (and) Trump ... but in the year of the outsiders, they sure are now." -Jamie Reuben, principal, Reuben Brothers

But Montanino doesn't think a "no" vote would lead to a collapse of Italy's banking sector. However, a further drop in confidence among investors could hinder the banks from getting the external financial support they're trying to get.

Whether Italy will have its own Brexit moment is a question being heavily debated. Italy's next national elections are set for 2018, but a vote could be set for sooner if Renzi experiences a tough defeat in the Dec. 4 referendum.

"If Renzi suffers a big loss, he can't continue easily. A 60-40 vote means Renzi will likely resign, and then it will depend on the parliament to figure out what to do next," said Montanino.

More worries about the euro zone's future

If Renzi were to resign, that could in turn bolster support for Italy's right-wing populist party, the Five Star Movement, which is headed by former comedian Beppe Grillo. The Five Star Movement has agitated for Italy to leave the euro zone. Such an outcome may seem like a long shot, but at this point investors and others around the world are slower to dismiss such wild-card events out of hand.

The December referendum "could precipitate a wider euro zone crisis. People may not have been looking seriously at this pre-Brexit (and) Trump ... but in the year of the outsiders, they sure are now," said Jamie Reuben, principal at investment fund Reuben Brothers and one of the founding members of Metro Bank UK.

The reaction among bond traders to a "no" vote could be a bit different. The Italian 10-year is currently on track for its worst month in nearly four years, yielding around 2.15 percent. Mizuho International says a "no" would cause near-term volatility, but it views that as the better outcome for 2017.

"'No' may mean that Renzi steps down, leaving Italy with a rather ineffective government, but that is not such a bad thing at times like this, when we need lower political risk, not higher. Moreover a 'no' vote offers Italy stability through until the 2018 general election," said Peter Chatwell, head of European rates strategy at Mizuho International.

Politics are not only a focal point for public investors but for venture capitalists as well.

Seedcamp founder Carlos Eduardo Espinal said that the wave of populism spreading over Europe has created anxiety around immigration and economic policies — two components of entrepreneurship seen as important for its ability to flourish.

"Investments might be affected depending on what kind of incentives (or hurdles) are put in place by governments post-election," said Espinal. "For example, as much as tax-relief has been super helpful in unlocking investment capital for new companies, a reversal of such policies ... might have an adverse effect. Additional measures, such as monetary policy, can also affect the value of an investor's worth, and thus change their tolerance for risk via new enterprises."