Like other works of Robert Boyle, The Sceptical Chymist had a long and difficult gestation. In February 1654 Hartlib referred to Boyle's writing a treatise ‘de Chemia et de Chymicis’. This was very likely the early version of The Sceptical Chymist to which Boyle referred in his ‘Author's preface’ of 1661:

The preface informs us that Boyle circulated the manuscript among ‘some learned men’, who received it favourably and prompted the author to ‘make it public’. A letter from Clodius answering Boyle's doubts about the nature of metalline mercuries leads us to infer that Boyle circulated the manuscript among members of the Hartlib Circle.

What is evidently a copy of this treatise, entitled ‘Reflexions on the experiments vulgarly alledged to evince the 4 peripatetique elements, or ye 3 chymicall principles of mixt bodies’, survives in Henry Oldenburg's commonplace book. It was published in 1954 by Marie Boas, who maintained that the treatise was written between 1651 and 1657. This dating has been questioned by Charles Webster, who suggested that analogies between Boyle's water culture experiments and those performed by Robert Sharrock in 1659 appeared to indicate that Boyle wrote his ‘Reflexions’ between 1659 and 1660.