The agency says prosecutors in the eastern province of Alicante are examining the Spanish citizens mentioned in a report by the US Anti-Doping Agency into Armstrong's doping activities.
The USADA report mentions Spanish doctors Luis Garcia del Moral and Pedro Celaya and trainer Pepe Marti.
The move comes just days after a Madrid court found doctor Eufemiano Fuentes guilty of endangering the health of athletes through blood doping.
The court suspended Fuentes' one-year sentence and ordered the destruction of evidence that could implicate more athletes.