Not necessarily. Some probiotics are shelf stable and do not need to be refrigerated. But many probiotics do require refrigeration. What’s important to understand is that refrigeration doesn’t equal efficacy. If the label indicates CFU counts “at the time of manufacture,” it means that the amount of live bacteria the product contained when it was bottled is not guaranteed at the time you consume it. Look for products that guarantee CFU counts through expiration, instead, regardless of whether they need refrigeration.