PROFUSA, INC. 179,272,293 Shares of Common Stock for Resale by the Selling Stockholders This prospectus supplement amends and supplements certain information contained in the prospectus dated May 4, 2026 (the“Prospectus”), which forms a part of our registration statement on Form S-1 (File No. 333-295364). The Prospectus and thisprospectus supplement relate to the offer and resale from time to time, of up to 179,272,293 shares of our Common Stock, par value$0.0001 per share (“the Common Stock”), by the selling stockholders identified in the Prospectus (the “Selling Stockholder”). TheCommon Stock being offered for resale consists of: i. Up to 150,568,827 shares of Common Stock by Ascent Partners Fund LLC, whom we refer to in this prospectus as“Ascent,” pursuant to a common stock purchase agreement, dated as of July 28, 2025 and amended on December 22, 2025,we entered into with Ascent, which we refer to in this prospectus as the ELOC Purchase Agreement; ii. Up to 20,027,859 shares of our Common Stock by Ascent issuable upon conversion of certain convertible promissorynotes, with an aggregate principal value of approximately $7.0 million as of the date of this prospectus (the “Ascent Notes,”and upon conversion, the “Ascent Conversion Shares”); iii. Up to 3,333,333 shares of our Common Stock by Ascent issuable upon exercise of that certain warrant, dated April 20,2026, issued to Ascent in connection with Amendment No. 4 to the PIPE Subscription Agreement (the “Ascent InducementWarrant”, and upon exercise, the “Ascent Inducement Warrant Shares”); and iv. Up to 5,342,274 shares of Common Stock by NorthView Sponsor I, LLC (the “Sponsor”) issuable upon conversion ofcertain convertible promissory notes, with an aggregate principal value of approximately $1.9 million (the “Sponsor Notes,”and upon conversion, the “Sponsor Conversion Shares”). We will not receive any of the proceeds from the sale of Common Stock by the Selling Stockholder. However, we mayreceive up to $100,000,000 in aggregate gross proceeds from sales of the Purchase Shares to Ascent that we may, in our discretion,elect to make, from time to time, pursuant to the ELOC Purchase Agreement. The Selling Stockholders may sell or otherwise dispose of the shares of Common Stock described in the Prospectus and thisprospectus in a number of different ways and at varying prices. The shares of Common Stock may be sold at fixed prices, at marketprices prevailing at the time of sale, at prices related to prevailing market price or at negotiated prices. This prospectus supplement is being filed to update and supplement the information in the Prospectus with the informationcontained in our Current Report on Form 8-K, filed with the SEC on May 8, 2026 (the “May 8 Current Report”), our Current Reporton Form 8-K, filed with the SEC on May 15, 2026 (the “May 15 Current Report”) and our Current Report on Form 8-K, filed with theSEC on May 18, 2026 (the “May 18 Current Report”). Accordingly, we have attached the May 8 Current Report, May 15 CurrentReport and May 18 Current Report to this prospectus supplement. Our common stock is listed on the Nasdaq Capital Market under the symbol “PFSA.” On May 15, 2026, the last sale price forour common stock as reported on the Nasdaq Capital Market was $0.45 per share. This prospectus supplement should be read in conjunction with the Prospectus, including any amendments or supplementsthereto, which is to be delivered with this prospectus supplement. This prospectus supplement is qualified by reference to theProspectus, including any amendments or supplements thereto, except to the extent that the information in this prospectus supplementupdates and supersedes the information contained therein. This prospectus supplement is not complete without, and may not be delivered or utilized except in connection with, theProspectus, including any amendments or supplements thereto. We are a “smaller reporting company” as defined under the federal securities laws and, as such, have elected to comply withcertain reduced public company reporting requirements for the Prospectus and this prospectus supplement and may elect to do so infuture filings. We are an “emerging growth company,” as defined in the Jumpstart Our Business Startups Act of 2012 (“JOBS Act”). As aresult, we are eligible to take advantage of certain reduced disclosure and other requirements that are otherwise applicable to publiccompanies. See further discussion below. Investing in our securities involves a high degree of risk. You should review carefully the risks and uncertaintiesdescribed under the heading“Risk Factors”section of the Prospectus, and under similar headings in any amendment orsupplements thereto, and in our most recent Annual Report on Form 10-K. Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved ofthesesecurities or passed upon the adequacy or accuracy of the Prospectus and this prospectus su