Standard Life Investment - a major investor in Royal Dutch Shell - has said it will oppose the oil company's proposed takeover of BG Group.
It said a weak outlook for oil prices plus risks for BG in Brazil could make the deal "value destructive for Shell shareholders."
Few investors or analysts have openly challenged the deal's strategic benefits for the firm.
Shell said it remained confident of winning the vote.
A Shell spokesman said: "We continue to believe we have the broad base of shareholder support we need for the deal to complete."
Shell has also won the support of Institutional Shareholder Services (ISS), an influential advisory firm, which recommended that Shell shareholders support the deal.
The firm announced its intention to buy BG - an oil and gas exploration company - in April 2015 for £47bn.
But Standard Life said on Friday that the risk of further oil price falls and tax and operational risks connected to BG's Brazilian assets make the deal undesirable.
"We have concluded that the proposed terms of the acquisition of BG are value destructive for Shell shareholders," said David Cumming, head of equities at Standard Life Investments.
Standard Life is the 11th largest holder of Shell's B shares, with a 1.7% stake.
Shell B shares make up the share component in the cash-and-share deal that is expected to be completed on 15 February.
Standard Life is also the 16th biggest shareholder in BG, according to data from Bloomberg.
ISS, which advises around 5% of Shell's medium and small shareholders, said it supported the deal "given the compelling strategic rationale, and the significant positive economics to be realised within a relatively short time frame."
Shell will become the world's top liquefied natural gas trader after the deal.
In December Shell said it would cut 2,800 jobs as a result of restructuring the companies into one unit.