People have been stopped from entering Amesbury Baptist Centre as a precaution after a man and a woman were discovered unconscious at a nearby property in the town on Saturday.
Officers believe the couple may have frequented the place of worship on Butterfield Drive before they fell ill. A staff member at the church told Premier the pair may have attended a hog roast event.
Both aged in their 40s, the man and woman are currently in a critical condition at Salisbury District Hospital.
Wiltshire Police said: "Wiltshire Police and partners have this evening declared a major incident after it is suspected that two people might have been exposed to an unknown substance in Amesbury.
Detectives have not yet established whether the pair are victims of a crime but they are keeping an "open mind".
Officials do not believe the wider public faces a "significant health risk".
A Public Health England spokesman said: "The current advice from PHE England, based upon the number of casualties affected, is that it is not believed that there is a significant health risk to the wider public.
"This will be continually assessed as further information becomes known".
The pair were found at an address on Muggleton Road in the south edge of Amesbury.
Officers initially thought the pair may have taken illegal drugs but additional tests are now being conducted.
The events come after ex-Russia spy Sergei Skripal and Yulia, his daughter, were poisoned in a suspected nerve agent attack eight miles away in Salisbury in March. Police are not linking the two incidents.
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