The analysis of milk yield data shows that high genetic merit dairy cows do not express their full production potential in autumn. Therefore, we focused on metabolic stress and inflammatory response in the dry and peripartum periods as possible causes thereof. It was our understanding that some cows could not cope with the stress imposed by their physiological and productive status by means of adequate adaptation strategies. Accordingly, this study highlights the noxious factors with a potential to affect cows in the above transition period: hot summer climate, adverse genetic traits, poor coping with unfavorable environmental conditions, outright production diseases and consequences thereof. In particular, the detrimental effects in the dry period of overcrowding, photoperiod change and heat stress on mammary gland development and milk production are highlighted in the context of the autumn low milk yield syndrome. The latter could be largely accounted for by a “memory” effect on the innate immune system induced in summer by diverse stressors after dry-off, according to strong circumstantial and indirect experimental evidence. The “memory” effect is based on distinct epigenetic changes of innate immunity genes, as already shown in cases of bovine mastitis. Following a primary stimulation, the innate immune system would be able to achieve a state known as “trained immunity”, a sort of “education” which modifies the response to the same or similar stressors upon a subsequent exposure. In our scenario, the “education” of the innate immune system would induce a major shift in the metabolism of inflammatory cells following their reprogramming. This would entail a higher basal consumption of glucose, in competition with the need for the synthesis of milk. Also, there is strong evidence that the inflammatory response generated in the dry period leads to a notable reduction of dry matter intake after calving, and to a reduced efficiency of oxidative phosphorylation in mitochondria. On the whole, an effective control of the stressors in the dry period is badly needed for better disease control and optimal production levels in dairy cattle.