2 3 In the 19 th century Francis Galton first reported that humans represent numbers on a 4 mental number line with smaller numbers on the left and larger numbers on the right. It has 5 been suggested that this orientation emerges as a result of reading/writing habits for both 6 words or numbers. Recent evidence in animals and infants in the first months of life has 7 challenged the primary role of language in determining the left-to-right direction of spatial-8 numerical association, SNA. However, the possibility that SNA is learnt by early exposure to 9 caregivers' directional biases is still open. Here we show that 55-hour-old newborns, once 10 habituated to a number (i.e., 12), spontaneously associated a smaller number (i.e., 4) with the 11 left side and a larger number (i.e., 36) with the right side of space. Moreover, SNA in neonates 12 was not absolute but relative. The same number (i.e., 12) was associated with the left side 13 whenever the previously experienced number was larger (i.e., 36), but with the right side 14 whenever the number was smaller (i.e., 4). Control on continuous physical variables showed 15 that the effect was specific of discrete magnitudes. Hence, soon after birth humans associate 16 smaller numbers with the left space and larger numbers with the right space. These results 17 constitute strong evidence that in our species SNA originates from pre-linguistic and 18 biologically precursors in the brain.19 20 21 SIGNIFICANCE STATEMENT 22 For human adults, the representation of number and space is profoundly intertwined. 23 Humans represent numbers on a left to right oriented Mental Number Line (MNL), with 24 small numbers located on the left and larger ones on the right. How do these connections 25 3 arise? Do we learn to associate numbers with space throughout cultural learning and social 1 interactions or is this association rooted in the biology of the human brain? We showed that 2 neonates spontaneously associate numbers with space. After being habituated to a certain 3 number, neonates associated a smaller number with the left and a larger number with the 4 right side. This evidence demonstrates that a predisposition to map numbers onto space is 5 rooted in human neural systems.6 7