Earlier Thursday morning, jurors reported they were unable to reach a unanimous decision on any of the three counts against Cosby.
"I want to reiterate how proud I am of each and every one of you", O'Neill said as he sent the jury back to the hotel.
They had listened to Andrea Constand testify that Cosby gave her what he initially claimed were "herbal pills" to "take the edge off" - the pills turned out to be prescription sedatives - and then assaulted her while she was incapacitated.
After a week long trial in Norristown, PA that started on June 5, the once beloved and much accused 79-year old actor is facing more than 10-years behind bars for three felony charges of second-degree aggravated indecent assault against the then Temple University employee.
Cosby's lawyers maintain Constand was a willing sexual partner.
A hung jury would be a clear victory for Cosby, who would avoid what could have been years in prison.
The jury went back to the deliberating room after having the quaaludes testimony read back to them and listening again to the definition of reasonable doubt, the threshold that prosecutors must cross to win a conviction.
"A quick verdict will not be a good thing for Cosby", says Stuart Slotnick, a NY criminal defense attorney who has been following the case for more than two years.
The jury has completed about 40 hours of deliberations, including three consecutive 12-hour days, without reaching an unanimous verdict and will return on Friday. If the panel can't break its impasse, O'Neill could declare a hung jury and a mistrial.
Constand sued in civil court, and Cosby provided a sworn deposition in which he said he had engaged in consensual sexual activity with Constand - and that he had obtained Quaaludes in order to give them to women with whom he wanted to have sex.
Several of the women, who have been awaiting a verdict all week, got into arguments with a number of Cosby supporters who appeared at the trial for the first time on Thursday.
The jury's note, delivered a few minutes after 11 a.m. on Thursday, raised the possibility that the closely watched case might end in a mistrial, leaving it to prosecutors to decide whether to seek a retrial.
"It's simply inappropriate at this time", O'Neill said.
Defense lawyers during the trial emphasized discrepancies in Constand's statements to police in 2005 in an effort to undermine her credibility.
O'Neill told jurors Thursday night, "I am proud of each and every one of you ... this is hard work you are doing".
Lili Bernard, another alleged Cosby sexual assault survivor, clashed with Cosby supporters outside the courthouse Thursday afternoon. Montgomery County District Attorney Kevin Steele, right, Montgomery County Assistant District Attorney Kristen, center, and Bill Cosby's defense attorney Angela Agrusa enter the courtroom during jury deliberat.
The case has already helped demolish Cosby's nice-guy reputation as "America's Dad".
Accuser Andrea Constand says Cosby drugged and molested her.
In his decade-old depositions, Cosby said he gave Constand Benadryl, a common allergy drug whose side effects can include drowsiness.
Jewel Allison, a former model who says Cosby assaulted her in the 1980s, faced off against a woman holding a sign that read "Bill Cosby is innocent" in capital letters.