The Orange County District Attorney's Office said in a statement Wednesday that 36-year-old Edgar Alfonso Lamas and 53-year-old Carlos Raygozaparedes have pleaded not guilty to six drug-related counts with enhancements.
If convicted on all charges, both men face a maximum sentence of 37 years and four months in prison.
Each man is being held on $5 million in bail. A preliminary hearing is set for June.
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Prosecutors say authorities pulled over the minivan leaving a Buena Park, California home on March 17.
According to the district attorney's office, a lethal dose of fentanyl is 2 milligrams. Authorities nabbed 20.5 pounds, which they say is enough to kill 4.7 million people.
Last November, the Orange County D.A. announced that a drug dealer or distributor of drugs could be charged with murder if it was determined their drug activities resulted in someone's death.
The Associated Press contributed to this report.