Some 30% of pre-weaning infants present problems of sleep during the night, especially those who are bottle-fed. The solution is for them to be breast-fed for as long as possible, or, if this is not possible, for the formula milk to reproduce breastmilk’s natural circadian variations in the concentrations of tryptophan and those nucleotides which have a beneficial effect in consolidating the circadian sleep–wake cycle. To study in pre-weaning infants the effect on nocturnal sleep of the administration of formula milk dissociated into its day/night components. A prospective study was carried out on 30 pre-weaning infants of 4–20 weeks in age who preferentially showed sleep problems. The day dissociated formula, administered from 06: 00–18: 00, had lower levels of tryptophan and carbohydrates, and higher levels of proteins together with cytosine-5P, guanosine-5P, and inosine-5P. The night dissociated formula, administered from 18: 00–06: 00, had lower levels of proteins and medium-chain triglycerides, higher levels of tryptophan and carbohydrates, together with adenosine-5P and uridine-5P. In a random, double-blind, design, three one-week diets were administered: Diet A (Control): normal initiation milk; Diet B: 06: 00–18: 00 normal initiation milk, 18: 00–06: 00 dissociated night formula; and Diet C: day/night formulas with the schedule given above. The sleep patterns were analyzed by means of actimeters (Actiwatch®). Statistical analysis consisted of an ANOVA with a Scheffe F-test, taking a value of p< 0.05 to be statistically significant. The children receiving the week of Diet C (with the day/night formulas in synchrony with the environment) showed increased hours of actual sleep (7.68±0.54 h vs. 6.77±0.12 h for the Diet A control) and improved sleep latency (0.44±0.04 h vs. 0.60±0.08 h for the Diet A control). The same children receiving the Diet B in another different week showed an improvement in sleep efficiency (76.43±3.4% vs. the Diet A control 69.86±0.94%) and sleep latency (0.45±0.04 h vs. the Diet A control 0.60±0.08 h) The parents also reported, in response to follow-up questions, an improvement in the sleep of their infants during the Diet C week. Day/night infant formula milks designed according to the principles of chrononutrition help to consolidate the sleep/wake rhythm in bottle-fed infants.