2000 mazda protege lx transmission slips when changing gears on more than one gear, when the overdrive button is on. When I turn off overdrive the transmission shifts fine without slipping. I put in a transmission solution that Napa reconmended with no change. Does this sound like a serious problem, and if so could I just run with overdrive off?

Transmission needs to be rebuilt. The band and/or servo have failed. This band is used in 2nd and OD.

.One of the most common causes of a slipping transmission is a low automatic transmission fluid level, also a dirty and/or clogged automatic transmission filter can impede the normal flow of automatic transmission fluid throughout an automatic transmission and cause the transmission to slip. Adequate, unobstructed transmission fluid flow is necessary for the optimal operation and function of an automatic transmission, including the function of the transmission bands and gears, two transmission components that routinely cause transmission slippage.Another cause would be faulty torque converter action and maladjusted transmission band.

you best bet is a transmission shop to check fluid pressure values,not one of those aamco type places,

You are going to need a transmission shop. Mazdas do not always throw codes. You have an early OBD transmission, which do not send out many codes.

it sound like there is a problem with the synchronizers and or the gears them selves. either way you will need to have the trans rebuilt before you can not put it into any gear.

Suggestion try to check if the release bearing of the transmission is still ok and check also the transmission oil level and if you need to change the transmission oil.

I’m happy to assist further over the phone at https://www.6ya.com/expert/ramy_d9e7ebea3891f482

Try changing the fuel filter. Many times fuel problems can be mistaken for transmission problems because the motor is starving for gas.

More than likely the synchronizers are going out,they allow you to move from gear to gear without damaging transmission.

try calling a junkyard and see if they will tell you the enterchange ok good luck

O/D light flashing is computer indicating an issue with the transmission -no surprise. Make sure the transmission fluid is still good (dosn't smell burnt, right level). Slipping could be the TCC (torque Converter clutch) - not a cheap part - but would only really slip in 4th gear (above 40 mph). Slipping before that could be numerous things in the trans (low fluid pressure, torque converter issues).
I would be tempted to replace the fluid anyhow, but there is a chance an expensive issue is starting to arise - and replacing the fluid on a failing transmission could cause it to fail 100% (or can fix it nearly 100%). These can be touchy transmissions, too much DIY without the right diagnostic tools can be bad. Not what you wanted to hear, and not an expert, but have had some expertise with these.hope that helps.